Just working through it. Cornish Mizzle-day so am particularly slow today :In bed: So some observations I guess:
'Cardiopulmonary exercise tolerance (ET) testing is an objective measurement of treatment efficacy for fatigue and is accepted as a regulatory standard for drugs ameliorating exertional fatigue by exhibiting an average improvement of at least a 6.5% in intra-group, placebo-adjusted ET [16][19].
The Phase III multi-center, double-blind, placebo controlled trial reported here uses ET as its primary endpoint and the reduction in drug usage for symptom relief as one of several secondary endpoints in the evaluation of rintatolimod in the treatment of CFS/ME.'
Ok. So in order to prove this drug was effective at reducing fatigue the results of ET had to exceed the average improvement of 6.5%. Doesn't seem much does it? I mean if you are bed-bound i.e. KPS 30 (see below), then it probably is but this assumes of course that fatigue is the most important measure of the condition.
Although, in addition, if (and I haven't yet seen this mentioned) the Ampligen removes PEM then any improvement above 6.5% would certainly be welcomed - as would sustained ET over a significant period.
Like Esther though, I have to ask why this drug is seemingly so effective. What is happening within the body to improve performance.
They do talk generally about Ampligen of course and I suppose I can look it up again specifically:
'The rationale for the initial trials with rintatolimod (Poly I:C12U) in CFS/ME were based on its recognized antiviral and immunomodulatory properties and as an inducer of interferon [13]. These properties are mediated by its activity as a selective toll-like receptor 3 (TLR-3) agonist in the induction of innate immune responses [14]. Toll-like receptors, as primordial transmembrane, pattern recognition receptors, trigger alarm signals against invading pathogens by modulating cytokine cascades.'
One of the inclusion criteria (other than KPS below) was:
'Ability to walk (minimum of 20 seconds) on the moving treadmill (grade=0%; belt speed=1 mph) on a minimum of two (2) occasions during the twelve (12) weeks immediately preceding study entry.'
The definition of 'severe' prompted me to look up the Karnosfky score. We were not talking bed-bound patients then:
KPS score 40-60 was needed for inclusion i.e.
100 Normal activity; no complaints; no evidence of disease.
90 Able to carry on normal activity; minor signs or symptoms of disease.
80 Normal activity with effort; some signs or symptoms of disease.
70 Cares for self, unable to carry on normal activity or do active work.
60 Requires occasional assistance but is able to care for most of needs.
50 Requires considerable assistance for daily care.
40 Disabled; unable to care for self, requires special care and assistance.
30 Severely disabled; bedridden although death is not imminent.
20 Very sick; hospitalization and/or nursing care is necessary; active support treatment is necessary.
10 Moribund; fatal processes progressing rapidly.
0 Dead.
'The primary endpoint was ET on a treadmill (Trackmaster TM 225, Full Vision, Inc., Newton, KS) with ECG monitoring performed by a team of exercise physiology specialists who traveled to each of the trial sites (Workwell Physiology Services, Inc., Ripon, CA). Secondary endpoints included changes in the use of concomitant medications to treat CFS/ME symptoms, Karnofsky Performance Score (KPS) (Table S3), Activities of Daily Living (ADL), and the Vitality and General Health Perceptions subscales from the Short Form 36-Health Survey (SF-36).'
'Patients underwent treadmill ET testing according to a standardized protocol (Table S4). Subjects rated their perceived exertion, generally considered to be a reliable indicator of fatigue [20], using the Borg Scale and progressed through stages successively until they could no longer continue.'
Presumably that means until they felt they could no longer continue. Is that objective enough? Is it better than say GET objectivity? I don't know.
Results then:
'By week 40, the rintatolimod cohort (n = 100) had a mean change increase in ET of 96 seconds to 672, corresponding to a group mean increase of 16.6% and an intra-patient mean increase of 36.5%.'
'In contrast, the placebo group (n = 108) increased ET by 28 seconds to 616 corresponding to an intra-group mean increase of 4.8% and an intra-patient mean increase of 15.2%.'
So - on this measure - Ampligen appears what 3-4 times more effective at improving ET than placebo. Not bad. Or roughly twice as effective on the 'intra-patient mean increase'.
'For the patients who completed all 40 weeks (Table 1B) of the study (n = 194), mean baseline ET was 583 seconds for the rintatolimod cohort (n = 93) compared to 587 seconds for the placebo group (n = 101). At week 40, the rintatolimod patients had increased mean ET by 108 seconds (18.6%) to 691 compared to an increase of 27 seconds (4.6%) to 614 in the placebo cohort. The placebo-adjusted, intra-group and intra-patient increases were 14.0% and 24.6%, respectively.'
So roughly 4 times again in terms of ET for those on the drug compared to those on placebo. Again, I wonder if this ability is maintained long-term.
Enough for now. Need a rest....