Rituximab Phase III - Negative result

[AngelM]

During the course of my years of ME/CFS, I was diagnosed with breast cancer, and my chemo cocktail included Rituximab, Methtrexate, and Prednizone, among other drugs. That was 33 years ago, and the one thing I thought remarkable, besides surviving, of course, was that between the chemo treatments I felt very well. For the next 18 years, I had no symptoms of CFS, and my life returned to normal. Unfortunately, CFS returned with a vengeance in 2001, and has waxed and waned since. Of course the dosage of these drugs when used in chemo therapy is very high, much higher, I imagine than that given to CFS patients during research trials.

I can’t mourn the loss of Rituximab as a miracle cure, because I only recently learned that it was being considered for use with CFS. And my personal experience with it is only anecdotal. But I can’t help but wonder if the low levels of Rituximab administered during clinical trials might not have affected the outcome negatively. Just a thought.

 

[deleder2k]

During the course of my years of ME/CFS, I was diagnosed with breast cancer, and my chemo cocktail included Rituximab, Methtrexate, and Prednizone, among other drugs. That was 33 years ago, and the one thing I thought remarkable, besides surviving, of course, was that between the chemo treatments I felt very well. For the next 18 years, I had no symptoms of CFS, and my life returned to normal. Unfortunately, CFS returned with a vengeance in 2001, and has waxed and waned since. Of course the dosage of these drugs when used in chemo therapy is very high, much higher, I imagine than that given to CFS patients during research trials.

I can’t mourn the loss of Rituximab as a miracle cure, because I only recently learned that it was being considered for use with CFS. And my personal experience with it is only anecdotal. But I can’t help but wonder if the low levels of Rituximab administered during clinical trials might not have affected the outcome negatively. Just a thought.

What a story! It could very well that you're given cyclophosphamide. I think that is standard for breast cancer.

I am baffled why so many is sure that rtx works. If it worked on say 15% it should have showed up in the study, shouldn't it? The study showed no difference between patients who got rtx and those who got saline water. I can't rule out that no single individual will respond to rtx, but a major study was done, and the results were beyond bad. That is were we're at. With that said, I look forward to reading the study and the sub-studies, but I urge everyone to stay realistic. Prof Edwards has called continuing rituximab a distraction. I think the fact that professor at UBC shut down his work because of the study is very telling... BUT cyclo study looks promising! There's a lot going on. And just to make my self clear; if someone finds out that rtx could work on say 5% of patients diagnosed with ME that would be great - but allocating limited resources does not seem wise. A lot of stuff going on metabolics, cyclo, the other sub studies ++

 

[JES]

@deleder2k There were responders to Rituximab in the phase 2 part of the trial, see the attached table below. About one third bounced from a very low physical functioning score to almost 100 during the treatment. It seems to me unlikely that someone with a physical functioning score of 5 or 10, like the first two patients in the table, at 15 week point went all the way up to 100 if it was just a placebo response. Of course it may be that both experienced a spontaneous remission, but that seems unlikely as well, given that the patients in question had been sick for 8 and 13 years respectively.

But I wouldn't disagree that cyclo is probably the more efficient treatment. The problem with cyclo is that it comes with side effects, even more than rituximab. I'm a bit skeptical that cyclo will ever become a sensible option for anything but perhaps the severe category of ME/CFS patients.

 

[Gingergrrl]

@deleder2k There were responders to Rituximab in the phase 2 part of the trial, see the attached table below. About one third bounced from a very low physical functioning score to almost 100 during the treatment. It seems to me unlikely that someone with a physical functioning score of 5 or 10, like the first two patients in the table, at 15 week point went all the way up to 100 if it was just a placebo response. Of course it may be that both experienced a spontaneous remission, but that seems unlikely as well, given that the patients in question had been sick for 8 and 13 years respectively.

I agree (but did not know enough about the statistics in phase 2 of the trial to comment). Thank you for explaining it @JES. If one third of patients went from a very low functioning score to almost 100 during the treatment (especially at the 15 week point), I cannot imagine how this is placebo if these patients were sick for 8-13 years pre- Rituximab.

To me this means that there is either a sub-group within ME/CFS that is ill because of B-cell driven autoimmunity, or there is a group that has both ME/CFS and a B-cell driven co-morbidity, or there is a completely misdiagnosed group with B-cell driven autoimmunity and no ME/CFS. Either way, identifying these people helps both the individual people and future research.

 

[Murph]

How Phase II got such good results and Phase III got such bad results is a mystery. Unofortunately for those of us who want Rituximab to be helpful, Phase III was the better-designed trial. It had a control group and the previous trial didn't.

I remain open-minded to the possibility Rituximab helps a sub-group, or the chance that Phase III was adminstered/analysed wrongly, but for now the information we have should tip us towards skepticism that Rituximab will be helpful.

I really would like to examine the data myself. I hope they release the paper soon!

 

[EtherSpin]

During the course of my years of ME/CFS, I was diagnosed with breast cancer, and my chemo cocktail included Rituximab, Methtrexate, and Prednizone, among other drugs. That was 33 years ago, and the one thing I thought remarkable, besides surviving, of course, was that between the chemo treatments I felt very well. For the next 18 years, I had no symptoms of CFS, and my life returned to normal. Unfortunately, CFS returned with a vengeance in 2001, and has waxed and waned since. Of course the dosage of these drugs when used in chemo therapy is very high, much higher, I imagine than that given to CFS patients during research trials.

I can’t mourn the loss of Rituximab as a miracle cure, because I only recently learned that it was being considered for use with CFS. And my personal experience with it is only anecdotal. But I can’t help but wonder if the low levels of Rituximab administered during clinical trials might not have affected the outcome negatively. Just a thought.

I think Ron Davis is using technology to test the effects of magnitudes higher doses of drugs like Rituximab on blood samples from CGS patients ?
Others with better reading comprehension can confirm - hopefully he didn't shelve the idea after the phase III by these guys

 

[Dan_USAAZ]

During the course of my years of ME/CFS, I was diagnosed with breast cancer, and my chemo cocktail included Rituximab, Methtrexate, and Prednizone, among other drugs. That was 33 years ago, and the one thing I thought remarkable, besides surviving, of course, was that between the chemo treatments I felt very well. For the next 18 years, I had no symptoms of CFS, and my life returned to normal. Unfortunately, CFS returned with a vengeance in 2001, and has waxed and waned since. Of course the dosage of these drugs when used in chemo therapy is very high, much higher, I imagine than that given to CFS patients during research trials.

Hi @AngelM,
From what I can tell, Rituximab did not exist 33 years ago. It appears to have been developed and patented in the late 90s (1997 – 1998), so has been around for only 20 years. The history I quote is from Wikipedia, so can’t verify its accuracy.

Is it possible you were on a different med with a similar name?

I apologize if I have misunderstood your medical timeline. Your history is very interesting and your use of Rituximab appears quite relevant, but the dates do not appear to align.

Thanks in advance for any clarification.
Dan

 

[Moof]

I'm pretty sure a relative was treated for lymphoma with a CD20 monoclonal antibody in the late '80s, as part of a clinical trial. I've just lost contact with her during a house move, so I can't ask for confirmation at the moment, but it must have been very similar to Rituximab. I helped her to research it, which was very difficult in the days before the internet; I was amazed when she mailed me to say that a drug with the same target was being talked about as a possible ME treatment.

I only mention it because it's possible that @AngelM had similar treatment as part of a trial. Her treatment was successful too, though it was absolutely brutal – no-one's ever quite the same after going through that, and she always said that if the cancer came back, she wouldn't necessarily put herself through it again. I've nothing but respect for survivors, I'm not sure I could do it.

 

[Daydreamer45]

I'm sorry to completely change the subject, but what did people think of the Ampligen trials, especially in comparison with the Rituxan trials? Or if there's another thread I should check out, feel free to direct me (I haven't been on here much and I find it a little confusing to navigate with my foggy brain)

I know an ME patient friend who has benefited from Rituxan, so I was disappointed by the trial news as well. I also believe its about better subgrouping.

 

[FMMM1]

I'm sorry to completely change the subject, but what did people think of the Ampligen trials, especially in comparison with the Rituxan trials? Or if there's another thread I should check out, feel free to direct me (I haven't been on here much and I find it a little confusing to navigate with my foggy brain)

I know an ME patient friend who has benefited from Rituxan, so I was disappointed by the trial news as well. I also believe its about better subgrouping.

There's a potential blood based diagnostic test; here's a details of the study [https://pubs.rsc.org/en/content/articlelanding/2018/an/c8an01437j/unauth#!divAbstract]. The test is based on the measurement of phenylalanine in blood cells. This group is currently conducting a larger study.

Once you have a diagnostic test then you can check interventions e.g. identify those with ME/CFS (currently defined by symptoms and the exclusion of other diseases) and test whether the intervention works. Using this test you would measure whether the levels of phenylalanine returned to normal.

@Daydreamer45 - if you Google "Ampligen" then this is one of the hits:
http://simmaronresearch.com/simmaro...-which-way-ampligen-the-fda-advisory-meeting/
If you Google "Ampligen + Phoenix" then you'll find a bunch of stuff on this site

Ron Davis has, from memory, tried out a bunch of drugs on the nanoneedle thing. So that may be a possible way to test Ampligen. One possible drug target is suramin (sleeping sickness drug). I think Ron Davis said that suramin was due to be manufactured in 2019 (possible source).

I've always felt that a single case of autoimmune ME/CFS would be important:
1) for you/your family member i.e. if they had the autoimmune form of ME/CFS;
2) for everyone with ME/CFS i.e. since it would provide an opportunity to identify the disease mechanism in ME/CFS.

The potential blood test is discussed on this site:
https://forums.phoenixrising.me/ind...g-raman-spectroscopy-me-association-uk.61380/

Suramin is discussed on this site:
https://forums.phoenixrising.me/ind...avis-tested-suramin-in-his-expirements.52096/

 

[deleder2k]

I know an ME patient friend who has benefited from Rituxan, so I was disappointed by the trial news as well. I also believe its about better subgrouping.

Perhaps Rituximab (Rituxan in Northern America, Mabthera in rest of the world) can help a very small subset, but it won't be many. Remember that the group who got Rituximab in the study did not get better than the group who got placebo. If, say, the placebo rate was 20% and the Rituximab rate of response was 35%, we would seen a positive result. We did not. There was no statistically significant difference with respect to the endpoint that was set before the trial was conducted. There was a researcher from Canada that was looking at subgroups. He was trying to predict a response. When he heard the news of the negative study results he stopped his work. He didn't see a reason to continue.

That does not rule out that an extremely small subset of patients have an effect, but Rituximab looks mostly dead at the moment. With that said; we need to look at the study results to get the full picture, but we know that if there was a difference in the Rituximab and placebo group, the study result would be positive. It was not.

 

[FMMM1]

Perhaps Rituximab (Rituxan in Northern America, Mabthera in rest of the world) can help a very small subset, but it won't be many. Remember that the group who got Rituximab in the study did not get better than the group who got placebo. If, say, the placebo rate was 20% and the Rituximab rate of response was 35%, we would seen a positive result. We did not. There was no statistically significant difference with respect to the endpoint that was set before the trial was conducted. There was a researcher from Canada that was looking at subgroups. He was trying to predict a response. When he heard the news of the negative study results he stopped his work. He didn't see a reason to continue.

That does not rule out that an extremely small subset of patients have an effect, but Rituximab looks mostly dead at the moment. With that said; we need to look at the study results to get the full picture, but we know that if there was a difference in the Rituximab and placebo group, the study result would be positive. It was not.

In general I agree that Rituximab is dead in the water.

Here's a possible blood based test for ME/CFS:
1) abstract: https://pubs.rsc.org/en/content/articlelanding/2018/an/c8an01437j/unauth#!divAbstract;
2) full paper: https://sci-hub.se/10.1039/C8AN01437J.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161229/

The test appears to support Chris Armstrong's, and Fluge and Mella's, findings of a switch in cellular energy production i.e. from glucose to amino acids such as phenylalanine. Basically the test shows that people with ME/CFS have high levels of phenylalanine in their blood cells. Fluge and Mella described ME/CFS as follows:
"According to this model, ME/CFS is caused by immune interference with an unidentified target, potentially a signaling factor, which ultimately causes metabolic dysfunction and induction of secondary rescue mechanisms [switch in cellular energy production]." So the change in energy production is a secondary effect; the question is what is the (upstream) cause?

The test classified people as being controls, or having ME/CFS, here's an extract: "A machine learning classification model achieved an accuracy rate of 98% correctly assigning Raman spectra to either the CFS group or the control group". So basically all of those with ME/CFS have this change in energy production. There's a larger study underway so possibly this 98% may drop. Within this group there may be autoimmune forms:
1) there cannot be a high percentage who have B-cell autoimmunity since Rituximab failed. E.g. if 98% had B-cell autoimmunity then Rituximab would not have failed [see deleder2k comments above];
2) potentially a high percentage could have T-cell autoimmunity. See Mark Davis's talk at the OMF Symposium 2017.

If you look at the approximately 2% of those who are currently classified as having ME/CFS, i.e. those who do not have change in energy production, then possibly there are autoimmune forms of ME/CFS within that group:
1) they could all have B-cell autoimmunity since the Rituximab trial would fail if only 2% had B-cell autoimmunity;
2) potentially a high percentage could have T-cell autoimmunity. See Mark Davis's talk at the OMF Symposium 2017.
Doctor Avindra Nath found one patient who was diagnosed with ME/CFS who had another illness [presentation at Invest in ME Conference 2018].

Someone said to me i.e. before Rituximab trial failed -- it's a cancer drug it wipes your immune cells ---.

Ron Davis has said [from memory] the system may be intact. I.e. Surinam reverses the cellular energy problem. If that's the case then that's good news.

I've written to the European Union Committee on the Environment, Public Health and Food Safety (ENVI) to see if they would lobby for funding to see if this blood based diagnostic test can be validated. The ENVI Committee are currently lobbying for funding for Lyme disease. The European Union has funded the development of a diagnostic test for Lyme [2 million euros/dollars]. They have not given any funding to ME/CFS. Here the thread on this site:
https://forums.phoenixrising.me/ind...ch-theyre-working-for-you.61516/#post-1001161

Grateful for any assistance you could give for lobbying e.g. writing to Members of the European Parliament. E.g. I only speak English so help with other languages would be appreciated.

 

[Gingergrrl]

If you look at the approximately 2% of those who are currently classified as having ME/CFS, i.e. those who do not have change in energy production, then possibly there are autoimmune forms of ME/CFS within that group:

I don't think I understand this part but is there a study that showed that approximately 2% of people who are classified with ME/CFS (but don't have issues with energy production) actually have an autoimmune form of ME/CFS, with B-cell autoimmunity, and those are the responders to Rituximab in the trial?

 

[FMMM1]

I don't think I understand this part but is there a study that showed that approximately 2% of people who are classified with ME/CFS (but don't have issues with energy production) actually have an autoimmune form of ME/CFS, with B-cell autoimmunity, and those are the responders to Rituximab in the trial?

Yea firstly I think @deleder2k explained the outcome of the rituximab trial very well. Rituximab wipes out antibody producing cd20 b-cells. As deleder2k said a trial like this will fail unless a high percentage of participants have a b-cell autoantibody disease. I.e. you could have a low level of b-cell autoantibody disease and a failed rituximab trial. In fact the answer with rituximab is to find auto-antibodies which cause the disease and then treat only those people e.g. with rituximab. The current auto-antibody tests are very poor i.e. false positives/negatives Ron Davis has proposed a way to improve them [https://www.omf.ngo/2018/02/12/tweak-assay-bolster-disease-detection-stanford-medicine-news-center/].

The separate study I referred to is a small scale study which indicates that you can diagnose ME/CFS using blood cells i.e. you measure an amino acid (phenylalanine) in the blood cells. High phenylalanine in your blood cells means means that you are using amino acids (e.g. phenylalanine) to produce energy (ATP) rather than glucose. This appears to result in the low energy state i.e. you get less ATP when you switch to this mode.

In effect this study may be a way of separating people with chronic fatigue:

• who have this change in cellular energy production (to using amino acids). This study found that 98% had switched to using amino acids;
• from those who do not have this change in cellular energy production (still using glucose). This study found that 2% had not switched to using amino acids.

If you look at the 2% then they could have anything e.g. a known b-cell autoantibody disease which responds to rituximab. To repeat, deleder2k said the rituximab trial will fail if there are a very low percentage of people with a b-cell autoantibody disease. I assume that the 2% estimate is based on a well controlled patient group. If you roll the test out, e.g. to everyone who presents at the local doctors surgery with chonic fatigue, then the percentage will be much higher.

It's a big day e.g. Phair is speaking (I assume) and he's looking at this cellular energy stuff.

As well as talking to each other on this site; why don't we try to talk to those who can actually fund the development of diagnostic tests/treatments etc - i.e. make a difference?

The European Union [EU] Committee on the Environment, Public Health and Food Safety (ENVI) are currently lobbying for increased funding for Lyme disease. The EU has already funded the development of a diagnostic test for Lyme disease i.e. 2 million euros/dollars. ME/CFS has received no EU funding. I've asked the Committee to lobby for funding for the development of a blood based diagnostic test for ME/CFS. See above, there appears to be a viable test available but we need validation studies. Here's a blog/thread on this site that I've been using [https://forums.phoenixrising.me/ind...h-theyre-working-for-you.61516/#post-1001161].

Try to influence those who can fund studies to develop diagnostic tests, treatments etc. E.g. European Union through elected members [members of the European Parliament] or the Senate/Representatives in USA.

 

[deleder2k]

Thanks, @FMMM1. Perhaps this is a task for the EMEA? European ME Alliance.

FMMM1; A (small) subset like myself benefit extremely from alcohol (ethanol). After drinking a lot all my pain vanishes, my dizziness almost disappears (!), I feel better in my stomach, my joints stop to crack, the pain fades away, and my muscle spasms goes away. I am 100% certain that it is ethanol. I've tried all sorts of alcohol, and it is not something in the red wine that may help like reservatrol. After an intake of say 1 litre of red wine I feel better for 24 hours.

If the body can't utilise glucose, then I guess it uses ethanol? I know that the researchers at Haukeland are aware of this, and they have been doing some DNA work at the lab, but I don't know if they've reached some sort of conclusion. What do you think about it? I've tried all sorts of supplements, a lot of different medicines, but the only things that REALLY work is alcohol. A few years ago I could not walk more than 100 metres without feeling muscle pain and lactic acid in my legs. After 0.5 litres of 40% vodka I walked 10 kilometres. The next morning wasn't that bad if you exclude the headache. 48 hours after the intake of alcohol I had a negative reaction.

 

[Gingergrrl]

If you look at the 2% then they could have anything e.g. a known b-cell autoantibody disease which responds to rituximab.

I haven't had time to follow any recent reports (and am not sure if this is new info?) but did the study find that the 2% who were responders actually had a B-cell driven autoantibody disease? I assume it wouldn't matter if it was a well-known disease or an unknown disease with obscure autoantibodies? I believe this is the group that I am in and why I was a responder (in general, I was not part of any study).

 

[deleder2k]

I haven't had time to follow any recent reports (and am not sure if this is new info?) but did the study find that the 2% who were responders actually had a B-cell driven autoantibody disease? I assume it wouldn't matter if it was a well-known disease or an unknown disease with obscure autoantibodies? I believe this is the group that I am in and why I was a responder (in general, I was not part of any study).

I'm not sure if that is what he meant...? 151 patients included in the study. That means that approx. 75 patients received Rituximab. 2% would then be 1 and a half patient. If there was in fact 2% response rate adjusted for placebo I don't think that that will tell us anything, unless the researchers doesn't find something in their analysis' that is compelling. But if it is, it would need to be researched more thoroughly.

I have not seen the manuscript for the RTX trial, but it will be interesting to read when the study is published. There's not reason to have high hopes for Rituximab, but the other research that was conducted in the same study will be extremely interesting. They've done A LOT of lab work. Their blood bank is huge. Combine the knowledge of dedicated ME researchers with a huge blood bank AND the computing power available in 2018. We are sure to say that much can and will happen.

 

[FMMM1]

I haven't had time to follow any recent reports (and am not sure if this is new info?) but did the study find that the 2% who were responders actually had a B-cell driven autoantibody disease? I assume it wouldn't matter if it was a well-known disease or an unknown disease with obscure autoantibodies? I believe this is the group that I am in and why I was a responder (in general, I was not part of any study).

The potential blood based diagnostic test for ME/CFS measures phenylalanine (an amino acid) in blood cells. The (small) study found that that approximately 2% of the study group did not demonstrate a switch to using amino acids as their primary energy source i.e. for these blood cells. A switch to using amino acids as your energy source would, to my limited knowledge, explain the low energy state in ME/CFS.

None of the participants in this study were treated with rituximab, or (to my knowledge were they) tested for autoimmune antibodies.

I think there could well be a small group of people who benefit from rituximab either because:

• they have an as yet unidentified autoimmune disease; or
• because rituximab is effective in another way. I am not talking about placebo. We don't understand the disease mechanism in ME/CFS; therefore, rituximab could have an indirect positive effect.

I think we should keep looking for autoimmune antibodies since the identification of antibodies would help to establish the disease mechanism and identify a (sub) group who would benefit from immune therapy.

Good luck to you.

Are the presentations from yesterdays OMF Symposium available on YouTube yet?

 

[Daydreamer45]

The potential blood based diagnostic test for ME/CFS measures phenylalanine (an amino acid) in blood cells. The (small) study found that that approximately 2% of the study group did not demonstrate a switch to using amino acids as their primary energy source i.e. for these blood cells. A switch to using amino acids as your energy source would, to my limited knowledge, explain the low energy state in ME/CFS.

None of the participants in this study were treated with rituximab, or (to my knowledge were they) tested for autoimmune antibodies.

I think there could well be a small group of people who benefit from rituximab either because:

• they have an as yet unidentified autoimmune disease; or
• because rituximab is effective in another way. I am not talking about placebo. We don't understand the disease mechanism in ME/CFS; therefore, rituximab could have an indirect positive effect

Are the presentations from yesterdays OMF Symposium available on YouTube yet?

Thank you for the info on the Ampligen trial. Based on the link, sounds like the research could’ve been done in a better manner and the FDA could’ve been more open minded (For lack of a better word)

I had no clue about the research into a new biomarker, and I appreciate the way you explained it to @Gingergrrl above. Exciting stuff!

 

[FMMM1]

Thanks, @FMMM1. Perhaps this is a task for the EMEA? European ME Alliance.

FMMM1; A (small) subset like myself benefit extremely from alcohol (ethanol). After drinking a lot all my pain vanishes, my dizziness almost disappears (!), I feel better in my stomach, my joints stop to crack, the pain fades away, and my muscle spasms goes away. I am 100% certain that it is ethanol. I've tried all sorts of alcohol, and it is not something in the red wine that may help like reservatrol. After an intake of say 1 litre of red wine I feel better for 24 hours.

If the body can't utilise glucose, then I guess it uses ethanol? I know that the researchers at Haukeland are aware of this, and they have been doing some DNA work at the lab, but I don't know if they've reached some sort of conclusion. What do you think about it? I've tried all sorts of supplements, a lot of different medicines, but the only things that REALLY work is alcohol. A few years ago I could not walk more than 100 metres without feeling muscle pain and lactic acid in my legs. After 0.5 litres of 40% vodka I walked 10 kilometres. The next morning wasn't that bad if you exclude the headache. 48 hours after the intake of alcohol I had a negative reaction.

Regarding the role of the European ME Alliance (EMEA); I know very little about the EMEA.

Phair, got involved in ME/CFS because his neighbours/friends were affected.

If you profiled those involved in Lyme then I guess you would find a group like Phair who had family/friends affected. Possibly you'd find some of those involved participate on the basis of "fairness" or rather perceived gender based unfairness. I haven't looked a Lyme but I guess it has the same issues regarding whether it's a real illness and being labelled as psychological women's disease.

If we want to see delivery then we need those who can direct public policy i.e. what gets funded. Lyme is better funded lets try to learn from them.

A senior adviser once asked what dictates the agenda? The European Commission type entity e.g. identifying key issues? Answer no. When they arrived in the office on a Monday morning the agenda could be what the person the Minister bumped into at the newsagent on Saturday said; true. Yes Minister (political comedy) is based in part on that.

Those who I've asked said that quite often what works is personal [Phair] or rational [cost 1 million people in Europe have ME/CFS]. Gender equality [perceived gender based unfairness] might not be the way to go.

I think there's a role for those who have ME/CFS and their family members and I think that they could possibly influence the decision makers. I don't see much of a downside i.e. risk of making it worse.

When you read the contributions on this site you will understandably find people who can't get treatment complaining. We need to try to put those systems in place. Check out Ron Davis's presentation at OMF Symposium he's highlighting the need to deliver a diagnostic test and demonstrating some options. I only watched part of Ron's presentation.

Be careful of alcohol. I'm not aware of anyone saying it's a potential fuel or that it has some other benefit.

We're all struggling with this; good luck.