A clinical trial of prednisone to empirically separate subgroups?

[Jesse2233]

One of the biggest issues facing clinical trials for ME is the heterogeneity of the condition even within strictly defined CCC parameters.

It occurred to me as I was brainstorming potential clinical trials that a high powered test of prednisone with careful before and after lab monitoring might be helpful in identifying subgroups.

Prednisone of course cannot be taken long term, but the results could be instructive for clinicians and researchers for subgroup biomarkers and further treatment investigations.

Some thoughts:

• Prednisone (and similar steroids) tends to produce a dramatic benefit for many immune mediated conditions not seen with other drugs
• Response to prednisone could serve as a rough indicator for primary immune involvement
• Strong response might indicate pure autoimmune / autoinflammatory etiology
• Weak response could indicate placebo or a degree of autoimmune / autoinflammatory etiology
• No response or long term worsening might indicate a chronic pathogen, pure mito dysfunction, organ damage (heart, brain, liver, CNS), systemic epigenetic alterations, hormonal dysfunction, something else, or some combination of the above
• Pre / post labs could include NKC function, cytokines, pathogen antibodies / PCRs, classic autoimmune markers, select autoantibodies (CellTrend, ACA, SMA, etc), viscosity/coagulation markers, plasma amino acids, organic urine acids, hormones, MRIs / PETs / SPECTs, other previously identified potential biomarkers (eg Activin B), as well as granular symptom checklists and emperical measures of severity (eg step count, orthostatics)
• Tracking of the above labs and correlation with clinical response might provide clues to subset biomarkers
• It would be interesting to then test the strongly responsive subgroup (or a new subgroup with their biomarkers) with immune modulating treatments like rituximab, IVIG, plasmapheresis, photopheresis, and CellCept
• It would be good to have a large sample size (~100) if many lab makers are tested
• Prednisone is extremely cheap, so drug cost for the trial wouldn’t be huge

 

[justy]

co morbidities could affect the results of this. For example, some of m symptoms improve a lot on prednisolone eg the MCAS ones, however i also have a general worsening, i dont get the good up effect, i get very ill and feel awful and lose my appetite.

Secondly a lot of us just dont tolerate steroids. I get steroid psychosis, suicidal ideation and severe confusion at just 5mg

But i see where you are going with this. Just think it wont be ass straightforward.

 

[Jesse2233]

@justy I agree, there could be a lot of confounding variables. But even so there could be data to glean from the noise

 

[Frenchguy]

I was on prednisone 0,5 mg/day with no effect during 6 months.

I think a poor response doesn't mean you don't have immune related disease.
In fact many autoimmune disease don't respond to Prednisone (many sjogren patients don't improve in the 3 symptoms class of the disease, sicca, fatigue, pain), but this disease is considered like a model of autoimmune diseases.

With the informations on cyclo trial, people seem to respond so maybe the immune activation can have a great impact on symptoms in ME.
Maybe we just don't understand at the moment the impact of this immune activation and the target of activated T cells.

I don't have to say that, but I think that a short prednisone trial would help some people diagnosed with ME, because they don't have ME.