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.
Original language | English |
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Pages (from-to) | 435-457 |
Number of pages | 24 |
Journal | Journal of Alzheimer's Disease |
Volume | 61 |
Issue number | 1 |
Early online date | 17 Nov 2017 |
DOIs | |
Publication status | Published - 28 Nov 2017 |
Keywords
- ADAS-cog
- Alzheimer’s disease
- amyloid protein
- clinical trial
- cohort study
- methylthioninium
- tau protein
- treatment
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Dive into the research topics of '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'. Together they form a unique fingerprint.Profiles
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Charles Harrington
- School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Senior Research Fellow
- Institute of Medical Sciences
Person: Academic Related - Research
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Gernot Riedel
- School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Personal Chair
- Institute of Medical Sciences
Person: Academic