先月ですけど、
今月の締めくくりにはコレ。
本編はかなりの長編です。
Potential of Low Dose Leuco-Methylthioninium Bis(Hydromethanesulphonate) (LMTM) Monotherapy for Treatment of Mild Alzheimer’s Disease: Cohort Analysis as Modified Primary Outcome
in a Phase III Clinical Trial
Journal of Alzheimer’s Disease xx (20xx) x–xx 1 DOI 10.3233/JAD-170560
IOS Press
Abstract.
Background:
LMTM is being developed
as a treatment for AD
based on inhibition of tau aggregation.
Objectives:
To examine the efficacy of LMTM
as monotherapy
in non-randomized cohort analyses
as modified primary outcomes
in an 18-month Phase III trial in mild AD.
Methods:
Mild AD patients (n = 800) were
randomly assigned to 100 mg twice a day
or 4 mg twice a day.
Prior to unblinding, the Statistical Analysis Plan was revised
to compare the 100 mg twice a day as monotherapy subgroup
(n = 79)
versus 4 mg twice a day as randomized
(n = 396),
and 4 mg twice a day as monotherapy
(n = 76)
versus 4 mg twice a day as add-on therapy
(n = 297),
with strong control of family-wise type I error.
Results:
The revised analyses were statistically significant at the required threshold
of p < 0.025 in both comparisons
for change in ADAS-cog, ADCS-ADL, MRI atrophy, and glucose uptake.
The brain atrophy rate was initially typical of mild AD in both add-on and monotherapy groups,
but after 9 months of treatment, the rate in monotherapy patients declined significantly to that reported for normal elderly controls.
Differences in severity or diagnosis at baseline between monotherapy and add-on patients did not account for significant differences in favor of monotherapy.
Conclusions:
The results are consistent with earlier studies in supporting the hypothesis that LMTM might be effective as monotherapy and that 4 mg twice a day may serve as well as higher doses.
A further suitably randomized trial is required to test this hypothesis.
