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P1–348: Pharmacokinetics of BIIB037 in people with mild‐to‐moderate Alzheimer's disease (AD) participating in a phase 1 dose‐escalation trial
Author(s) -
Ferrero Jim,
Stella Heather,
Leitermann Kate,
Mikulskis Alvy,
Song Tao,
Sevigny Jeff
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.05.574
Subject(s) - pharmacokinetics , cohort , medicine , dosing , placebo , senile plaques , amyloid beta , pharmacology , disease , gastroenterology , pathology , alzheimer's disease , alternative medicine
Background:A phase II 12-month trial of resveratrol for mild-moderate dementia due to Alzheimer’s disease (AD) will determine its safety and tolerability and putative effects on clinical outcomes, volumetric MRI, Aband tau levels in cerebrospinal fluid, and metabolic profiles. A history of metabolic syndrome or type 2 diabetes mellitus (T2D), particularly during midlife, is a well-known risk factor for AD in late life but underlying mechanisms are unknown.Methods: Exclusionary criteria include individuals consuming any resveratrol-containing supplement and subjects treated for T2D. Eligible subjects (50-90 year old men and women recruited from and/or referred to specialty clinics) with mild-moderate AD (MMSE 1226) were administered a baseline oral glucose tolerance test (OGTT, 75 g) after an overnight fast. Results will be compared to a repeat OGTT on the maximally tolerated resveratrol dose after 12 months. Resveratrol was synthesized, encapsulated, and packaged by Aptuit Laurus (now Catalent), initiated at 500 mg bymouth once daily, and will end with 1 g twice daily (with 500 mg increments every 3 months). Results: Five subjects (5/128 or 4%) revealed impaired fasting glycemia (110-125 mg/dl) and 38 subjects (38/ 125 or 30%) revealed impaired glucose tolerance at 2 hours (140-200 mg/ dl). Three subjects (3/128 or 2%) had findings consistent with a diagnosis of T2D (fasting glucose > 125 mg/dl) and 16 subjects (16/125 or 13%) had results consistent with T2D (glucose > 200 mg/dl) at 2 hours. The mean fasting glucose (+/S.E.) was 92 +/1 mg/dl. The mean glucose at 2 hours was 143 +/5 mg/dl. These data revealed a prevalence of impaired fasting glycemia or T2D at baseline of 6%. The prevalence of impaired glucose tolerance or T2D at 2 hours was 43%. Six subjects screen-failed due to newly-diagnosed or treated T2D.Conclusions:Due to this high prevalence, the OGTT may be considered for individuals with AD in order to optimize medical management of borderline or undiagnosed T2D. AD, a chronic inflammatory disorder may increase risk of co-incident impaired fasting glycemia, glucose intolerance, and T2D. Conversely, a glucoregulatory disturbance may promote AD. Treatment of this study cohort with resveratrol or placebo is in progress.