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18-Month Study of Curcumin

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of California, Los Angeles
Sponsor:
Information provided by (Responsible Party):
Gary Small, MD, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT01383161
First received: June 22, 2011
Last updated: August 1, 2014
Last verified: August 2014

June 22, 2011
August 1, 2014
March 2012
July 2016   (final data collection date for primary outcome measure)
Change in cognitive testing results from Baseline to 6, 12 and 18 months. [ Time Frame: 6, 12 and 18 months. ] [ Designated as safety issue: No ]
People with age-related cognitive decline (i.e., MCI, AAMI or normal aging), who receive curcumin 90 mg twice each day will show less evidence of cognitive decline (as measured with neuropsychological assessments) than those receiving placebo after 18 months.
Change from baseline in amount of abnormal amyloid protein deposits [ Time Frame: 18 months ] [ Designated as safety issue: No ]
People with age-related cognitive decline (e.g., MCI, AAMI or normal aging) who receive a daily dietary supplement (curcumin) along with healthy lifestyle counseling (proper nutrition, exercise, etc.), will show less build-up of abnormal amyloid protein deposits (as measured with FDDNP-PET imaging) than those receiving placebo after eighteen months.
Complete list of historical versions of study NCT01383161 on ClinicalTrials.gov Archive Site
  • Correlation of primary outcomes to gentoype [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Cognitive change, FDDNP-PET measures, and treatment response will vary according to genotypes found to influence age at dementia onset (e.g., apolipoprotein E [APOE] TOMM40).
  • Change in level of inflammatory markers in blood from Baseline to 18 months. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    People with age-related cognitive decline, who receive curcumin 90 mg twice each day, will show decreased measures of inflammation in the blood compared with those receiving placebo after 18 months.
  • Change in amount of brain amyloid protein in subjects received curcumin from Baseline to 18 months. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    People with age-related cognitive decline who receive an oral dose of curcumin 90 mg twice each day will show less build-up of plaques and tangles (as measured with FDDNP-PET imaging) than those receiving placebo after 18 months.
Changes from baseline in memory and cognitive testing scores [ Time Frame: 9 and 18 months ] [ Designated as safety issue: No ]
People with age-related cognitive decline (e.g., MCI, AAMI or normal aging) who receive a daily dietary supplement curcumin will show less evidence of future cognitive decline than those receiving placebo eighteen months.
Not Provided
Not Provided
 
18-Month Study of Curcumin
18-Month Double-Blind, Placebo-Controlled Study of Curcumin

This project is designed to study the effects of the dietary supplement curcumin on age-related cognitive impairment. In particular, the study seeks to determine the effects of curcumin on cognitive decline and the amount of abnormal amyloid protein in the brain. Genetic risk will also be studied as a potential predictor of cognitive decline.

Subjects will be randomly assigned to one of two treatment groups: either a placebo or the curcumin supplement (465 milligrams of Theracurmin™ of which 30 mg is curcumin). The investigators expect the people receiving the curcumin supplement to show less evidence of decline and fewer after 18 months than those receiving the placebo. The investigators believe cognitive decline and treatment response will vary according to a genetic risk for Alzheimer's.

The investigators will study 132 subjects with memory complaints aged 50-90 years. Initially, subjects will undergo a clinical assessment, an MRI and a blood draw to determine genetic risk and to rule out other neurodegenerative disorders linked to memory complaints. Subsequently, subjects will undergo an -(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP)PET scan and a baseline neuropsychological assessment to confirm MCI or normal aging diagnosis. Once enrolled, subjects will begin taking the supplement (either curcumin or a placebo), and be asked to return every three months for regular MRIs and review sessions. Every 6 months, subjects will also neuropsychological assessments. At the conclusion of the study, subjects will be asked to complete a final neuropsychological assessment, MRI scan, PET scan and blood draw. Additional blood will be drawn at baseline and at 18 months and frozen to assess inflammatory markers if outcomes are positive.

FDDNP-PET scans will be used to measure the amount of abnormal amyloid plaque- and tau tangle- proteins in the brain; the MRIs will be used to monitor supplement side effects and measure brain structure; the neuropsychological assessments will monitor rates of cognitive decline; the blood draws will be used to test levels of inflammatory markers.

Several lines of evidence suggest that the neuropathological and clinical decline leading to Alzheimer disease (AD) begins years before patients develop the full AD clinical syndrome (NINCDS-ADRDA diagnostic criteria; McKhann et al, 1984). Mild memory complaints build gradually years before patients develop dementia. The neuropathological hallmarks of AD, "preclinical" neuritic plaques (Braak & Braak, 1991) and neurofibrillary tangles (Price & Morris, 1999), are also present years prior to clinical diagnosis. These abnormal protein deposits correlate strongly with cognitive decline.

Preclinical amyloid deposits may begin decades prior to dementia onset. In fact, diffuse plaques in non-demented elderly persons are associated with an accelerated age-related cortical cholinergic deficit, consistent with preclinical AD (Beach et al, 1997; Arai et al, 1999). Also consistent with a prolonged preclinical disease stage is our own work showing that position emission tomography (PET) measures of cerebral glucose metabolism vary according to AD genetic risk (apolipoprotein E-4 [APOE-4]) and predict cerebral metabolic and cognitive decline in people with mild cognitive complaints (age-associated memory impairment [AAMI]; Small et al, 2000). Such observations have stimulated interest in preclinical AD markers or biomarkers of brain aging that may assist in tracking treatments of AAMI and related conditions. New PET imaging methods now make it possible to provide in vivo measures of cerebral amyloid neuritic plaques (e.g., florbetapir-PET; Clarke et al, 2011) and tau neurofibrillary tangles (e.g. FDDNP-PET; Small et al, 2006, 2009).

Despite these previous research findings, clinical trials (including those using biomarkers as response measures) and subsequent treatment recommendations have been limited to patients with the full clinical dementia syndrome or mild cognitive impairment (MCI), a condition that increases the risk for developing dementia (Petersen et al, 2001). Cholinesterase inhibitors are currently the only drugs that have FDA clearance for treatment of AD, but previous studies (e.g., Ringman et al, 2005) suggest that other interventions, such as dietary or herbal supplements, may benefit cognition, and possibly interrupt the accumulation of abnormal amyloid protein deposits in the brain. For example, curcumin (diferulomethane), a low molecular weight molecule with antioxidant and anti-inflammatory activities that is derived from dietary spice, may have both cognitive-enhancing and anti-amyloid properties (Ringman et al, 2005; Yang et al, 2005).

To address such issues, we propose to build upon our group's previous longitudinal brain imaging and genetic risk studies in people with age-related memory decline. Because previous studies suggest that curcumin may improve cognitive ability and prevent the build-up of age-associated plaques and tangles in the brain, we will perform a double-blind, placebo-controlled trial of curcumin to test the following hypotheses:

  1. People with age-related cognitive decline (i.e., MCI, AAMI or normal aging),, who receive curcumin 90 mg twice each day will show less evidence of cognitive decline (as measured with neuropsychological assessments) than those receiving placebo after 18 months.
  2. People with age-related cognitive decline who receive an oral dose of curcumin 90 mg twice each day will show less build-up of plaques and tangles (as measured with FDDNP-PET imaging) than those receiving placebo after 18 months.
  3. People with age-related cognitive decline, who receive curcumin 90 mg twice each day, will show decreased measures of inflammation in the blood compared with those receiving placebo after 18 months.
  4. Cognitive change, FDDNP-PET measures, and treatment response will vary according to genotypes found to influence age at dementia onset (e.g., apolipoprotein E [APOE] TOMM40).

Because curcumin may alter inflammatory markers in the blood, we will draw blood samples at baseline and at 18 months and freeze them for later analyses.

To test theses hypotheses, up to 132 subjects, with age-related cognitive decline will be enrolled (Crook et al, 1986; Petersen et al, 2001). Subjects will be randomized, using a double-blind design, to one of two treatment groups: curcumin (three 30 mg capsules twice each day) or placebo, and followed for 18 months. FDDNP-PET scanning will be performed at baseline and at 18 months. Magnetic resonance imaging (MRI) scans also will be performed for co-registration of PET and assistance in identifying regions of interest. Neuropsychological assessments will be performed at baseline, 6 months, 12 months and at the conclusion of the clinical trial (18 months). Blood will be drawn at baseline to perform genotyping.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
  • Age-associated Cognitive Impairment
  • Mild Cognitive Impairment (MCI)
  • Drug: Curcumin
    Six 465 milligram capsules (containing 30 mg of curcumin each) per day for 18 months.
    Other Name: Theracurmin CR-031P™ (Dietary Supplement)
  • Other: Placebo
    Six 465 milligram capsules per day for 18 months.
    Other Name: Placebo
  • Active Comparator: Curcumin
    Theracurmin (180mg/day)
    Intervention: Drug: Curcumin
  • Placebo Comparator: Sugar Pill
    Intervention: Other: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
132
July 2017
July 2016   (final data collection date for primary outcome measure)

Inclusion Criteria

  1. Agreement to participate in the 18-month double-blind, placebo-controlled clinical trial of curcumin.
  2. Diagnostic criteria for mild cognitive impairment (MCI) or any age related memory decline according to standard criteria (Petersen et al, 2001; Crook et al, 1986).
  3. Age 50 to 90 years.
  4. No significant cerebrovascular disease: modified Ischemic Score of < 4 (Rosen et al, 1980).
  5. Adequate visual and auditory acuity to allow neuropsychological testing.
  6. Screening laboratory tests and EKG without significant abnormalities that might interfere with the study.

Exclusion Criteria

  1. Diagnosis of probable Alzheimer's disease (AD) or any other dementia (e.g., vascular, Lewy body, frontotemporal) (McKhann et al, 1984).
  2. Evidence of other neurological or physical illness that can produce cognitive deterioration. Volunteers with a history of stroke, TIA, carotid bruits, or lacunes on MRI scans will be excluded.
  3. Inability to undergo MRI.
  4. Evidence of Parkinson's disease as determined by the motor examination (items 18-31) of the Unified Parkinson's Disease Rating Scale (Fahn et al, 1987).
  5. History of myocardial infarction within the previous year, or unstable cardiac disease.
  6. Uncontrolled hypertension (systolic BP > 170 or diastolic BP > 100).
  7. History of significant liver disease, clinically-significant pulmonary disease, diabetes, or cancer.
  8. Current diagnosis of any major psychiatric disorder according to the DSM-IV TR criteria (APA, 2000).
  9. Current diagnosis or history of alcoholism or substance addiction.
  10. Regular use of any medication that may affect cognitive functioning including: centrally active beta-blockers, narcotics, Clonidine, anti-Parkinsonian medications, antipsychotics, benzodiazepines, systemic corticosteroids, medications with significant cholinergic or anticholinergic effects, anti-convulsants, or Warfarin. Occasional chloral hydrate use will be allowed, but discouraged, for insomnia.
  11. Use of more than one multivitamin per day. Vitamins other than the standard multivitamin supplement will not be allowed.
  12. Use of medications known to affect FDDNP-PET binding (e.g., ibuprofen, naproxen).
  13. Use of more than one daily baby aspirin (81mg) and/or use of any medication containing curcumin.
  14. Use of cognitive enhancing supplements (e.g. Ginkgo biloba).
  15. Use of any investigational drugs within the previous month or longer, depending on drug half-life.
  16. Pregnancy.
  17. HIV infection.
  18. Evidence of vasogenic edema; specifically, evidence of more than 4 cerebral microhemorrhages (regardless of their anatomical location or diagnostic characterization as "possible" or "definite") or a single area of superficial siderosis), or evidence of a prior macrohemorrhage at screening or baseline.
Both
50 Years to 90 Years
No
Contact: Natacha Donoghue, M.A. 310-206-7392 ndonoghue@mednet.ucla.edu
Contact: Jackie Martinez, M.S. 310-206-1319 jacquelinemartinez@mednet.ucla.edu
United States
 
NCT01383161
11-001740, IND 112714
Yes
Gary Small, MD, University of California, Los Angeles
University of California, Los Angeles
Not Provided
Principal Investigator: Gary W Small, M.D. UCLA Longevity Center
University of California, Los Angeles
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP