• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Phase III trial of antiviral + antinflammatory combo

Messages
93
wow! since my pain level is so excruciating I am so happy to read a possible treatment. Thanks for posting the info and any follow ups to come. It may not be the best but at this point anything that cuts the pain is welcome.
 

Wally

Senior Member
Messages
1,167
Since it is Cox-2 they are inhibiting here, I am wondering about plain old ibuprofen?

@natasa778,

Perhaps the longer plasma half life of Celebrex versus Ibuprofen might make a difference in how these two NSAIDs effect inflammation.

-Ibuprofen has a plasma half life of 1.8 to 2 hrs. Ibuprofen inhibits both COX-1 and COX-2.
See, 1) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191627-/ and 2) http://www.drugs.com/ppa/ibuprofen.html

-Celebrex has a plasma half life of approximately 11 hrs. See, http://www.drugs.com/pro/celebrex.html
At therapeutic levels Celebrex has been found to only inhibit COX-2 and is the only drug on the market in the U.S. that acts in this way. See, 1) http://www.medscape.com/viewarticle/563829_2 and
2) http://en.wikipedia.org/wiki/Celecoxib

Instead of using Ibuprofen, I wonder if Naproxen would be more effective as an OTC anti-inflammatory choice because of this drug's longer plasma half life of 12 to 17 hrs. However, Celebrex would still have an edge over Naproxen in its ability to only inhibit COX-2. See, 1) http://www.rxlist.com/naprosyn-drug/clinical-pharmacology.htm and 2) http://www.ncbi.nlm.nih.gov/pubmed/15229960

You might also want to take a look at a report published by Consumers Report, which provides a lot of information about many of the NSAIDs, including their potential side effects and estimated cost (January 2013). See, http://www.consumerreports.org/health/resources/pdf/best-buy-drugs/Nsaids2.pdf
 
Last edited:

ukxmrv

Senior Member
Messages
4,413
Location
London
@natasa778,


Instead of using Ibuprofen, I wonder if Naproxen would be more effective as an OTC anti-inflammatory choice because of this drug's longer plasma half life of 12 to 17 hrs. However, Celebrex would still have an edge over Naproxen in its ability to only inhibit COX-2. See, 1) http://www.rxlist.com/naprosyn-drug/clinical-pharmacology.htm and 2) http://www.ncbi.nlm.nih.gov/pubmed/15229960

Wally and Natasha,

That is what my GP is hoping. He has given me a prescription for Naproxen to see if it has the same good effects (with the Valtrex).

It's too soon to tell for me.
 

voner

Senior Member
Messages
592
here is the abstract of Dr. Pridgens ACR 2014 paper:

1878 - A Combination of Celecoxib and Famciclovir Is Efficacious in the Treatment of Fibromyalgia: Results of a Phase IIa Randomized, Double-Blind, Placebo-Controlled Study
Monday, November 17, 2014: 4:30 PM
104 B (Boston Convention and Exhibition Center)
Presentation Number: 1878

William Pridgen1, Carol Duffy2, Judith Gendreau3 and R Michael Gendreau3, 1Innovative Med Concepts, Tuscaloosa, AL, 2University of Alabama, Tuscaloosa, AL, 3Gendreau Consulting, LLC, Poway, CA

Background/Purpose:
Fibromyalgia (FM) is a common chronic pain syndrome with symptoms that include widespread pain, fatigue, sleep disruption and cognitive impairment. It is known that infections and other types of stressors are capable of triggering the development of FM. We hypothesize that these stressors could be responsible for triggering a reactivation of latent herpesviruses, and that this reactivation could in turn lead to the central nervous system dysregulation seen in this condition. The present study was designed to evaluate an anti-viral drug combination selected for activity against herpes class viruses.

Methods:

A total of 143 patients selected using the ACR 2010 FM criteria were enrolled at 12 sites in a 16-week, double-blind, placebo-controlled trial. Patients were randomized (1:1) to receive a proprietary combination of celecoxib + famciclovir or placebo. Outcome measures included a 24-hour recall pain numeric rating scale (NRS), Fibromyalgia Impact Questionnaire (FIQ-R), Patient Global Impression of Change (PGIC), and the PROMIS fatigue short form at baseline, and after 6, 12 and 16 weeks of study participation.

Results:

The primary efficacy endpoint was change in pain from baseline. Pain reduction was evaluated using the pain NRS and the 7-day recall pain item from the FIQ-R. Change from baseline was determined using an MMRM approach with LOCF/ BOCF imputation for missing data. A significant decrease in pain was observed for patients on treatment vs. placebo at 16 weeks by both measures. The absolute change on the NRS was -1.9 units vs -1.1, comparing active to placebo (p=0.031). On the FIQ-R item, the change was -2.2 vs -0.92 (p=0.001). Key secondary endpoints included analysis of the PGIC, where a value of “1” or “2” was considered a clinical responder. Significantly improved PGIC response rates were noted at endpoint: 33.3% for active vs 19.2% in placebo patients (p=0.031). Total FIQR score change at the endpoint visit was -17.54 vs -7.87 (p=0.002), while changes in the 3 domains were 14.29 vs -5.44 (p=0.004) for Function, -4.29 vs -1.89 (p=0.003) for Overall Impact, and -16.77 vs -7.90 (p=0.004) for Symptoms. In addition, improvements in fatigue were seen at endpoint on the PROMIS fatigue (-7.62 units vs -4.15; p=0.020).

The safety profile was especially encouraging. Despite the celecoxib component, gastrointestinal and nervous system treatment emergent adverse events were reported significantly more often in the placebo treatment group (GI: 29.0% vs 42.5%; nervous system: 17.4% vs 23.3%; active to placebo), and study completion rates favored active treatment over placebo (82.6% vs. 60.8%) (largely driven by higher placebo discontinuation rates due to adverse events and lack of efficacy).

Conclusion:

A proprietary combination of famciclovir, which we postulate is inhibiting herpesvirus replication, and celecoxib, known to inhibit both herpesvirus replication and reactivation, was efficacious in treating multiple symptoms of FM. Given the simultaneous improvement in many domains and the surprising tolerability of this combination of drugs, we believe this combination warrants further study as a potential new therapy for fibromyalgia patients.


Keywords: fibromyalgia and viruses

Disclosure:W. Pridgen, Innovative Med Concepts, Innovative Med Concepts ; C. Duffy, Innovative Med Concepts, Innovative Med Concepts ;J. Gendreau, Innovative Med Concepts ; R. M. Gendreau, Innovative Med Concepts, Innovative Med Concepts.

I also posted this at this other thread:
http://forums.phoenixrising.me/inde...-dr-carol-duffy-name.29206/page-9#post-524896
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Pridgen et al. said:
Key secondary endpoints included analysis of the PGIC, where a value of “1” or “2” was considered a clinical responder. Significantly improved PGIC response rates were noted at endpoint: 33.3% for active vs 19.2% in placebo patients (p=0.031).
I'm hesitant about introducing a note of negativity/caution here, but these results don't look impressive to me.
If I've understood this correctly, only an extra 14.1% of participants responded to treatment, over and above the placebo group, using this particular outcome measure. And that doesn't mean that the participants, who responded, experienced a major response or a transformation in their health.
However, the safety profile seems quite good.
 
Last edited:

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Very underwhelming results. Subjective outcome measures. If a psychobabbler had presented these outcomes in the context of a psychological intervention, people would be (rightly) very critical.
This would never do in a phase III study. I am unsure about whether or not its acceptable in a phase II study.

PS It was however placebo controlled, and double blinded. That is way above psychobabble standards. I am very unhappy with subjective outcomes in general, but if this is taken as only being about quality of life and not cure it might be appropriate. While pain is difficult to measure currently, they can probably deal with fatigue objectively if they want to.
 
Last edited:

natasa778

Senior Member
Messages
1,774
reposting this from another thread, could be relevant to this study as showing improved T cell-dependent functions after 12 weeks of celecoxib.


Researchers at the University of Oslo and Oslo University Hospital have recently published a study indicating that treatment with celecoxib, an anti-inflammatory drug commonly used to treat pain and arthritis, can improve the outcomes for HIV patients...

...
The blood of HIV patients tends to have high amounts of lipopolysaccharide (LPS), a bacterial component usually restricted to the digestive tract in healthy individuals. This LPS activates the enzyme COX2, which then triggers a series of events that can result in chronic immune activation. In a 12 week clinical study, researchers discovered that blocking this enzyme in HIV patients with COX-2 inhibitors can decrease immune activation and improve responses to HIV-relevant vaccines.


To test the effectiveness of COX-2 inhibitors in HIV patients, various markers of chronic immune activation were compared between treated and non-treated patients. The primary endpoint was the density of CD38, a marker of chronic immune activation, on T cells. The significant decrease in CD38 seen in the HIV patients treated with COX-2 inhibitors likely correlates to a slower depletion of CD4+ T cells and therefore a slower progression to AIDS.

Other markers of chronic immune activation were also shown to improve after treatment, such as decreased PD-1 expression, increased numbers of regulatory T cells and lower levels of antibodies (IgA).


www.ncmm.uio.no/news/cox-2-inhibitors-and-hiv.html
 

Jonathan Edwards

"Gibberish"
Messages
5,256
I'm hesitant about introducing a note of negativity/caution here, but these results don't look impressive to me.
If I've understood this correctly, only an extra 14.1% of participants responded to treatment, over and above the placebo group, using this particular outcome measure. And that doesn't mean that the participants, who responded, experienced a major response or a transformation in their health.
However, the safety profile seems quite good.

I agree Bob. We seem to have two threads on this. As indicated on the other thread my concern is that this trial gives no evidence that the famvir had anything to do with it, since there is no celecoxib alone arm. I fear it will go down like a lead balloon at ACR.

Celecoxib increases risk of stroke and cardiac events and I think has been withdrawn in UK as mentioned. If Cox-2 inhibition is needed this looks like a catch-22.
 

Wally

Senior Member
Messages
1,167
I am not sure if the article linked below has previously been posted in one of the threads related to anti-inflammatory drugs or brain inflammation, but I thought it gives an interesting overview of how a drug like Celebrex and other NSAIDs may work in regards to brain inflammation. Many more possibilities than just inhibition of COX-2.

Non-Steroidal Anti-Inflammatory Drugs and Brain Inflammation: Effects on Microglial Functions
http://www.google.com/url?sa=t&rct=...=awJXPkZGPUzCAI6Drju6Aw&bvm=bv.79908130,d.cGE
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Celecoxib increases risk of stroke and cardiac events and I think has been withdrawn in UK as mentioned. If Cox-2 inhibition is needed this looks like a catch-22.

Back in the 90s when I was put on Vioxx I commented that this class of drug was dangerous, and this was predictable from the biochemistry. I have always considered all COX-2 inhibitors to be dangerous, though more because higher doses than are used for general NSAIDs are given as these are more effective and do not pose a danger to the GIT. However they work by shutting down two entire hormone branches. That is not safe if used regularly at anything other than low doses. I have never taken this class of drug other than as once only treatment for acute pain, such as severe headache.

There are reasons to think ME patients may have problems with eicosanoid regulation. So long term use may be a risk, even if effective in other ways.
 

CFS_for_19_years

Hoarder of biscuits
Messages
2,396
Location
USA
Not trying to take this thread on another tangent, but since there might be benefits from taking COX-2 inhibitors, and NSAIDs have some many bad side effects, I thought perhaps people here might like to see a list of natural COX inhibitors. I looked for some lists by Googling, and one report I found was a scientific journal article:

Natural anti-inflammatory agents for pain relief
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3011108/
Because of the significant side effect profiles of steroidal and NSAID medications, there is a greater interest in natural compounds, such as dietary supplement and herbal remedies, which have been used for centuries to reduce pain and inflammation.[94] Many of these natural compounds also work by inhibiting the inflammatory pathways in a similar manner as NSAIDs. In addition to the COX pathway, many natural compounds act to inhibit nuclear factor-kB (NF-kB) inflammatory pathways.

Some of the natural remedies listed are:
Omega-3 EFAs (fish oil)
White willow bark

Curcumin (turmeric)
Green tea
Pycnogenol (maritime pine bark)
Boswellia serrata resin (Frankincense)
Resveratrol
Uncaria tomentosa (cat’s claw)
Capsaicin (chili pepper)



 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
I find capsaicin can help (but I do not use it now for other reasons), I have had benefit from pycnogenol at high dose, omega-3s are obvious, and resveratrol may have saved my life. There are alternatives, but generally they are less powerful. Its the power of high dose COX-2 inhibitors that make them work better, they very much shut down the COX-2 isoform, but this also create worse side effects, including sudden death. Effectiveness and side effects go together.

As an analogy, and don't try this at home especially if you have ME, drinking alcohol can dull pain. A sip will have some effect. A glass more. A bottle even more. Enough bottles that you cannot even raise a glass may almost completely dull your pain. Its also the dose most likely to do serious damage and possibly kill you.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
NSAIDs, is that they interfere in the healing process

I know that NSAIDs block healing in the gut from action on COX-1, which is why gastric ulcers are a common side effect. I am less sure about other tissues, but then again damaging the gut is cause enough. Someone I know had to have emergency surgery to fix a gastric rupture due to NSAIDs.

Now NSAIDs do block a wide range of hormones that are essential to regulating all sorts of things, as they block most eicosanoids.

Unfortunately no pain killing drug is really safe. They all have problems. Natural substances also cause problems. Very often a natural treatment at high enough dose to have equivalent effect might cause equivalent problems. It depends on mechanisms.

Non drug treatments have some promise. Even listening to music to take your mind off things can work. Cold packs and hot packs often work, but not well on ME/fibro muscle pain. There are some meditations designed for pain as well, but I have not explored that much.

As a rule of thumb the power of the pain relief is in proportion to the risk.

Treatments targeting the cause of the pain are a better way to go ... if you know what the cause is.
 

JT1024

Senior Member
Messages
582
Location
Massachusetts
While I totally agree with concerns with COX-2 inhibitors everyone has expressed above, I can honestly say I've taken substantially more OTC (ibuprofen) with little to no relief.

My initial and current dosage of Celebrex is 200 mg with Valtrex 500 mg, twice a day. I had minimal relief from pain with the Celebrex. The addition of Valtrex resulted in 90% relief of pain and disability for several days at the beginning of treatment. I now know the dosages are not optimal and the Valtrex is not the optimal antiviral.

Would I take another combination of anti-inflammatory/anti-viral knowing risky side effects to have any semblance of a normal life again?? HELL YEAH!!!

My life has been reduced to the point where enjoying simple things is difficult. I suspect almost everyone on this forum can relate to that.
 

Wally

Senior Member
Messages
1,167
Here is an interesting article regarding the use of aspirin to enhance the effects of treatment for schizophrenia. Celebrex was also reviewed as part of this study, but it was not found to have a significant effect on the treatment.
Aspirin shown to benefit schizophrenia treatment

Some anti-inflammatory medicines, such as aspirin, estrogen, and Fluimucil, can improve the efficacy of existing schizophrenia treatments, new research suggests. Research has shown that the immune system is linked to certain psychiatric disorders, such as schizophrenia and bipolar disorder. Research has shown that "antioxidants and anti-inflammatory drugs could not only reduce symptoms associated with the disorders but also prevent the appearance of neurobiological abnormalities and transition to psychosis if given early during brain development," experts say.

. . . Schizophrenia in particular is linked to the HLA gene system, which is found on chromosome 6 in humans. The HLA system controls many of the characteristics of the immune system.

According to lead researcher, Professor Iris Sommer (Psychiatry Department, University Medical Centre, Utrecht, Netherlands): "The picture on anti-inflammatory agents in schizophrenia has been mixed, but this analysis pulls together the data from 26 double-blind randomised controlled trials, and provides significant evidence that some (but not all) anti-inflammatory agents can improve symptoms of patients with schizophrenia. In particular, aspirin, estrogens (in women) and the common antioxidant N-acetylcysteine (fluimicil) show promising results. Other anti-inflammatory agents, including celecoxib, minocycline, davunetide, and fatty acids showed no significant effect." . . .

Click on this link to continue reading the article. http://www.sciencedaily.com/releases/2014/10/141020090144.htm
 
Last edited:

Snow Leopard

Hibernating
Messages
5,902
Location
South Australia
So basically, they've shown that a class of painkiller has modest effect on pain in Fibromyalgia patients?

While it is not the most exciting treatment in the world, it is certainly better than nothing.