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.
J Alzheimers Dis
; 61(1): 435-457, 2018.
Article
in En
| MEDLINE
| ID: mdl-29154277
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 (nâ=â800) were randomly assigned to 100âmg twice a day or 4âmg twice a day. Prior to unblinding, the Statistical Analysis Plan was revised to compare the 100âmg twice a day as monotherapy subgroup (nâ=â79) versus 4âmg twice a day as randomized (nâ=â396), and 4âmg twice a day as monotherapy (nâ=â76) versus 4âmg twice a day as add-on therapy (nâ=â297), with strong control of family-wise type I error.RESULTS:
The revised analyses were statistically significant at the required threshold of pâ<â0.025 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 4âmg twice a day may serve as well as higher doses. A further suitably randomized trial is required to test this hypothesis.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antipsychotic Agents
/
Treatment Outcome
/
Alzheimer Disease
/
Methylene Blue
Type of study:
Clinical_trials
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Etiology_studies
/
Incidence_studies
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Observational_studies
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Risk_factors_studies
Limits:
Aged
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Aged80
/
Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
J Alzheimers Dis
Journal subject:
GERIATRIA
/
NEUROLOGIA
Year:
2018
Document type:
Article
Affiliation country: