Curcumin in Patients With Mild to Moderate Alzheimer's Disease

A Phase II, Double-Blind, Placebo-Controlled Study of the Safety and Tolerability of Two Doses of Curcumin C3 Complex Versus Placebo in Patients With Mild to Moderate Alzheimer's Disease

The purpose of this study is to examine the safety and tolerability of curcumin, and to determine its effect on patients with mild to moderate Alzheimer's Disease (AD).

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Dietary supplement: Curcumin C3 Complex

Detailed Description

Curcumin, a yellow substance found in the spice Turmeric, has antioxidant, non-steroidal anti-inflammatory (NSAID), and cholesterol-lowering properties, all of which make it a good candidate in the prevention and treatment of AD. The study will examine the safety and tolerability of 2 different doses of curcumin C3 complex. Blood and cerebrospinal fluid (CSF) tests will be used to examine how the curcumin is absorbed in the body, and whether it has an effect on inflammation, oxidative damage, and cholesterol levels. Participants will also be tested to determine the potential effect of curcumin on cognition, behavior, and daily function in patients with mild to moderate AD.

Participants will be randomly assigned to receive one of two doses of curcumin, or a placebo, for the initial 6 months of the trial. For the final 6 months, those receiving a placebo will be switched to one of the two doses of the drug. The 33 participants will make 7 visits to the study site over a 12-month period. These visits may include a physical and neurological examination, routine laboratory tests, lumbar puncture, and neuropsychological (mood and memory) evaluations.

• Study Type: Interventional
• Enrollment (Anticipated): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Westwood, California, United States
      • UCLA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female at least 50 years old
• Diagnosis of probable AD
• No history of significant psychiatric or non-AD neurological disease
• Proficient in English to be able to perform cognitive testing
• Caregiver available to monitor and administer medication and to accompany patient to every clinical visit
• On stable doses of cholinesterase inhibitors and memantine (Alzheimer's medications) for 3 months prior to enrollment
• On stable doses of all other allowed medications for at least one month prior to starting the study medication

Exclusion Criteria:

• Current or recent major psychiatric illness (i.e. bipolar disorder, schizophrenia)
• Significant, uncontrolled systemic illness (i.e. chronic renal failure, chronic liver disease, poorly controlled diabetes, or poorly controlled congestive heart failure)
• Recent history of gastrointestinal bleeding or ulceration
• Alcoholism or substance abuse within the past year
• Familial, autosomal dominant Alzheimer's disease due to a mutation in a known gene (Presenilin-1, Presenilin-2, or Amyloid Precursor Protein)
• NSAIDs (e.g. ibuprofen, naproxen, etc.) taken on a regular basis (more than 3 times per week)
• Aspirin at doses more than 325 mg per day
• Coumadin, heparin, other anticoagulants
• Antioxidants or other supplements including gingko biloba, coenzyme Q10, alpha-lipoic acid
• Vitamin E at doses more than 2,000 IU per day
• Vitamin C at doses more than 500 mg per day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Side effect checklist

Secondary Outcome Measures

Outcome Measure
Oxidative damage
Inflammation/gliosis
A-beta levels
Tau levels
Total plasma cholesterol, LDL and HDL; ApoE
Plasma curcumin and metabolites
Cognitive and behavioral measures

Collaborators and Investigators

• Sponsor: John Douglas French Foundation
• Collaborators: Institute for the Study of Aging (ISOA)
• Investigators: Study Director: John Ringman, MD, University of California, Los Angeles

Publications and helpful links

General Publications

• Chandra V, Pandav R, Dodge HH, Johnston JM, Belle SH, DeKosky ST, Ganguli M. Incidence of Alzheimer's disease in a rural community in India: the Indo-US study. Neurology. 2001 Sep 25;57(6):985-9. doi: 10.1212/wnl.57.6.985.
• Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci. 2001 Nov 1;21(21):8370-7. doi: 10.1523/JNEUROSCI.21-21-08370.2001.
• Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005 Feb 18;280(7):5892-901. doi: 10.1074/jbc.M404751200. Epub 2004 Dec 7.
• Ringman JM, Frautschy SA, Teng E, Begum AN, Bardens J, Beigi M, Gylys KH, Badmaev V, Heath DD, Apostolova LG, Porter V, Vanek Z, Marshall GA, Hellemann G, Sugar C, Masterman DL, Montine TJ, Cummings JL, Cole GM. Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimers Res Ther. 2012 Oct 29;4(5):43. doi: 10.1186/alzrt146. eCollection 2012.

Study record dates

Study Major Dates

• Study Start: July 1, 2003
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: December 17, 2004
• First Submitted That Met QC Criteria: December 17, 2004
• First Posted (Estimate): December 20, 2004

Study Record Updates

• Last Update Posted (Estimate): December 3, 2009
• Last Update Submitted That Met QC Criteria: December 2, 2009
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Keywords: Cholesterol; anti-inflammatory; Turmeric; NSAID; Curcumin; anti-oxidant; Curry
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Curcumin
• Other Study ID Numbers: IA0065