Safety Study of Nicotinamide to Treat Alzheimer's Disease

• ClinicalTrials.gov Identifier: NCT00580931
• Recruitment Status: Completed
• First Posted: December 27, 2007
• Last Update Posted: January 25, 2017
• Sponsor: University of California, Irvine
• Collaborator: Alzheimer's Association
• Information provided by (Responsible Party): Steven Schreiber, University of California, Irvine

Study Description

Brief Summary:

The purpose of this study is to determine whether nicotinamide, or vitamin B3, is safe and effective in the treatment of Alzheimer's disease.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Drug: Nicotinamide; Drug: Enduramide placebo	Phase 1; Phase 2

Detailed Description:

The goal of this proposal is to show that, nicotinamide (NA), a B3 vitamin, is safe and effective for the treatment of patients with mild to moderate Alzheimer's disease (AD). NA is known to block the ability of certain proteins to regulate other proteins by removing their acetyl groups. Recent evidence has demonstrated that inhibitors such as NA prevent nerve cell degeneration in models of Huntington's disease (HD), Parkinson's disease and Lou Gehrig's disease (or ALS). Despite these beneficial effects in many different animal models, there have been no studies to date using these inhibitors in AD. In some of our recent studies we found that the potent inhibitor, NA, significantly improves learning and memory in transgenic mice that develop AD. NA treatment also resulted in striking changes in tau, a protein that abnormally accumulates in AD. NA has been extensively used in clinical studies over the last 40 years and is generally safe and well-tolerated. As NA is a safe and readily available vitamin supplement, our recent results provide a strong argument for a study of NA in patients with AD. We therefore propose to treat 50 patients with mild to moderate AD with either NA (1500 milligrams twice a day) or an identical but inactive drug (placebo) for 24 weeks. At 6 week intervals we will assess functions such as learning and memory, and ability to carry out daily activities as well as caregiver reports using standardized tests. We will also perform spinal taps at the beginning and end of the study to measure the level of abnormal tau protein in the cerebrospinal fluid. Blood tests will periodically be done to assess liver function and complete blood counts. The results of this study may provide the basis for a more extensive study of NA for the treatment of mild to moderate AD.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy of Nicotinamide for the Treatment of Alzheimer's Disease
• Actual Study Start Date: January 2008
• Actual Primary Completion Date: July 2014
• Actual Study Completion Date: July 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; Subjects will receive experimental drug in a blinded fashion.	Drug: Nicotinamide; 1500 mg twice a day for 6 months; Other Name: Enduramide
Placebo Comparator: 2; Identical in size, shape and color to experimental drug.	Drug: Enduramide placebo; 1 tab twice a day

Outcome Measures

Primary Outcome Measures :

1. Alzheimer's Disease Assessment Scale-Cognitive Subscale [ Time Frame: Baseline, 6 wk, 12 wk, 18 wk, 24 wk ]

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 95 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of probable AD according to DSM-IV criteria
• Mild to moderate dementia based on Mini-Mental State Examination [MMSE] score between 13-25
• Minimum age 50 years
• Brain imaging (computed tomographic scan or magnetic resonance image) within 12 months consistent with a diagnosis of probable AD
• Hachinski Ischemic Score of <4.
• Stable doses of concomitant medications, including cholinesterase inhibitors (ChEIs) and/or memantine.

Exclusion Criteria:

• Dementia due to another cause
• Other neurological or psychiatric diseases
• Pseudodementia
• Unstable medical condition
• Initial treatment within 30 days of screening with a ChEI, memantine or any investigational drug
• History of alcoholism, drug abuse, liver disease, peptic ulcer disease
• Pregnancy, or the potential to become pregnant.

Contacts and Locations

Locations

United States, California

UC Irvine School of Medicine

Irvine, California, United States, 92697

Sponsors and Collaborators

University of California, Irvine

Alzheimer's Association

Investigators

• Principal Investigator: Steven S Schreiber, MD; Regents of the University of California

More Information

• Responsible Party: Steven Schreiber, Professor of Neurology, University of California, Irvine
• ClinicalTrials.gov Identifier: NCT00580931
• Other Study ID Numbers: IIRG-07-61197
• First Posted: December 27, 2007
• Last Update Posted: January 25, 2017
• Last Verified: January 2017

Keywords provided by Steven Schreiber, University of California, Irvine:

nutraceutical, dementia, cognition, HDAC inhibitor

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Niacinamide; Niacin; Nicotinic Acids; Vitamin B Complex; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Vasodilator Agents