18-Month Study of Memory Effects of Curcumin

NCT01383161 | Completed Phase 2 Results DMC

• 2 other identifiers: 11-001740IND 112714
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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 twice daily or the curcumin supplement (Theracurmin®, containing 90 mg of curcumin). The investigators expect that the volunteers receiving the curcumin supplement will show less evidence of decline after 18 months than those receiving the placebo. The investigators predict that cognitive decline and treatment response will vary according to genetic risk for Alzheimer's. The investigators will study 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 a diagnosis of MCI or normal aging. Once enrolled, subjects will begin taking the supplement (either curcumin or a placebo). Some of the initial subjects will be asked to return every three months for regular MRIs. Every 6 months, subjects will also receive 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 cognitive 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 determine genetic risk and to test levels of inflammatory markers.

Conditions

Age-associated Cognitive Impairment; Mild Cognitive Impairment (MCI)

Keywords

Curcumin; Turmeric; Memory; Cognitive Impairment; Brain Imaging; Supplement

Outcome Measures

Primary Outcomes (4)

• Change From Baseline to 18 Months on Brief Visual Memory Test-Revised, Recall

  The Brief Visual Memory Test-Revised (BVMT-R) provides a measure of visual memory. In three learning trials, the respondent views 6 geometric figures for 10 seconds and is asked to draw as many of the figures as possible from memory in their correct location on a page in the response booklet. A Delayed Recall Trial is administered after a 25-minute delay. Recall measures standard scoring of designs for accuracy and correct placement across the three trials. Scores across the three trials are summed and range from 0 to 36, with higher scores indicating better learning. There are 6 equivalent alternate forms.

  Baseline and 18 Months

• Change From Baseline to 18 Months on Brief Visual Memory Test-Revised, Delay

  The Brief Visual Memory Test-Revised (BVMT-R) provides a measure of visual memory. In three learning trials, the respondent views 6 geometric figures for 10 seconds and is asked to draw as many of the figures as possible from memory in their correct location on a page in the response booklet. A Delayed Recall Trial is administered after a 25-minute delay. Delayed recall measures standard scoring of designs for accuracy and correct placement after delay period. Scores range from 0 to 12 and reflect recent, long-term learning, with higher scores indicating better learning. There are 6 equivalent alternate forms.

  Baseline and 18 Months

• Change From Baseline on Buschke Selective Reminding Task, Consistent Long-Term Retrieval

  Buschke Selective Reminding Task (SRT) is a standardized measure of verbal learning that presents 12 words to the subject who is asked to immediately recall as many words as possible. The examiner then presents words that the subject was unable to recall until the subject can recall all 12 words without prompting twice, or until the examiner has presented prompts up to 12 times. Consistent Long-Term Retrieval score is the number of words that the subject recalls without receiving prompts and indicates how well the subject consolidates the new information during the learning phase (encoding). Scores indicate the sum of consistent long-term word retrieval across the 12 trials and range from 0 to 144, with higher scores indicating better learning.

  Baseline and 18 Months

• Change From Baseline on Buschke Selective Reminding Task, Total Score

  Buschke Selective Reminding Task (SRT) is a standardized measure of verbal learning that presents 12 words to the subject who is asked to immediately recall as many words as possible. The examiner then presents words that the subject was unable to recall until the subject can recall all 12 words without prompting twice, or until the examiner has presented prompts up to 12 times. Total Recall score is the sum of words recalled over the 12 trials, which reflects immediate recall (short-term memory) for new information. Scores range from 0 to 144, with higher scores indicating better learning.

  Baseline and 18 Months

Secondary Outcomes (2)

• Change From Baseline to 18 Months on Trail Making Test, Part A

  Baseline and 18 Months

• Change From Baseline to 18 Months on Beck Depression Inventory (BDI)

  Baseline and 18 Months

Study Arms (2)

Curcumin

ACTIVE COMPARATOR

Theracurmin (180mg/day)

Drug: Curcumin

Placebo

PLACEBO COMPARATOR

Sugar Pill

Other: Placebo

Interventions

Curcumin DRUG

Six Theracurmin capsules (containing 30 mg of curcumin each) per day for 18 months.

Also known as: Theracurmin CR-031P™ (Dietary Supplement)

Curcumin

Placebo OTHER

Six capsules per day for 18 months.

Also known as: Sugar Pill

Placebo

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Agreement to participate in the 18-month double-blind, placebo-controlled clinical trial of curcumin.
• 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).
• Age 50 to 90 years.
• No significant cerebrovascular disease: modified Ischemic Score of \< 4 (Rosen et al, 1980).
• Adequate visual and auditory acuity to allow neuropsychological testing.
• Screening laboratory tests and EKG without significant abnormalities that might interfere with the study.

You may not qualify if:

• Diagnosis of probable Alzheimer's disease (AD) or any other dementia (e.g., vascular, Lewy body, frontotemporal) (McKhann et al, 1984).
• 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.
• Inability to undergo MRI.
• 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).
• History of myocardial infarction within the previous year, or unstable cardiac disease.
• Uncontrolled hypertension (systolic BP \> 170 or diastolic BP \> 100).
• History of significant liver disease, clinically-significant pulmonary disease, diabetes, or cancer.
• Current diagnosis of any major psychiatric disorder according to the DSM-IV TR criteria (APA, 2000).
• Current diagnosis or history of alcoholism or substance addiction.
• 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.
• Use of more than one multivitamin per day. Vitamins other than the standard multivitamin supplement will not be allowed.
• Use of medications known to affect FDDNP-PET binding (e.g., ibuprofen, naproxen).
• Use of more than one daily baby aspirin (81mg) and/or use of any medication containing curcumin.
• Use of cognitive enhancing supplements (e.g. Ginkgo biloba).
• Use of any investigational drugs within the previous month or longer, depending on drug half-life.

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

UCLA Longevity Center

Los Angeles, California, 90095, United States

Location

Related Publications (13)

• Arai T, Ikeda K, Akiyama H, Haga C, Usami M, Sahara N, Iritani S, Mori H. A high incidence of apolipoprotein E epsilon4 allele in middle-aged non-demented subjects with cerebral amyloid beta protein deposits. Acta Neuropathol. 1999 Jan;97(1):82-4. doi: 10.1007/s004010050958.

  PMID: 9930898 BACKGROUND

• Beach TG, Honer WG, Hughes LH. Cholinergic fibre loss associated with diffuse plaques in the non-demented elderly: the preclinical stage of Alzheimer's disease? Acta Neuropathol. 1997 Feb;93(2):146-53. doi: 10.1007/s004010050595.

  PMID: 9039461 BACKGROUND

• Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239-59. doi: 10.1007/BF00308809.

  PMID: 1759558 BACKGROUND

• McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984 Jul;34(7):939-44. doi: 10.1212/wnl.34.7.939.

  PMID: 6610841 BACKGROUND

• Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review) [RETIRED]. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001 May 8;56(9):1133-42. doi: 10.1212/wnl.56.9.1133.

  PMID: 11342677 BACKGROUND

• Price JL, Morris JC. Tangles and plaques in nondemented aging and "preclinical" Alzheimer's disease. Ann Neurol. 1999 Mar;45(3):358-68. doi: 10.1002/1531-8249(199903)45:33.0.co;2-x.

  PMID: 10072051 BACKGROUND

• Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, Thibodeau SN, Osborne D. Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med. 1996 Mar 21;334(12):752-8. doi: 10.1056/NEJM199603213341202.

  PMID: 8592548 BACKGROUND

• Shoghi-Jadid K, Small GW, Agdeppa ED, Kepe V, Ercoli LM, Siddarth P, Read S, Satyamurthy N, Petric A, Huang SC, Barrio JR. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry. 2002 Jan-Feb;10(1):24-35.

  PMID: 11790632 BACKGROUND

• Small GW, Ercoli LM, Silverman DH, Huang SC, Komo S, Bookheimer SY, Lavretsky H, Miller K, Siddarth P, Rasgon NL, Mazziotta JC, Saxena S, Wu HM, Mega MS, Cummings JL, Saunders AM, Pericak-Vance MA, Roses AD, Barrio JR, Phelps ME. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6037-42. doi: 10.1073/pnas.090106797.

  PMID: 10811879 BACKGROUND

• Small GW, Mazziotta JC, Collins MT, Baxter LR, Phelps ME, Mandelkern MA, Kaplan A, La Rue A, Adamson CF, Chang L, et al. Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. JAMA. 1995 Mar 22-29;273(12):942-7.

  PMID: 7884953 BACKGROUND

• [No authors listed] Consensus report of the Working Group on:

  BACKGROUND

• Small GW, Rabins PV, Barry PP, Buckholtz NS, DeKosky ST, Ferris SH, Finkel SI, Gwyther LP, Khachaturian ZS, Lebowitz BD, McRae TD, Morris JC, Oakley F, Schneider LS, Streim JE, Sunderland T, Teri LA, Tune LE. Diagnosis and treatment of Alzheimer disease and related disorders. Consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer's Association, and the American Geriatrics Society. JAMA. 1997 Oct 22-29;278(16):1363-71.

  PMID: 9343469 BACKGROUND

• Salloway S, Sperling R, Gilman S, Fox NC, Blennow K, Raskind M, Sabbagh M, Honig LS, Doody R, van Dyck CH, Mulnard R, Barakos J, Gregg KM, Liu E, Lieberburg I, Schenk D, Black R, Grundman M; Bapineuzumab 201 Clinical Trial Investigators. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology. 2009 Dec 15;73(24):2061-70. doi: 10.1212/WNL.0b013e3181c67808. Epub 2009 Nov 18.

  PMID: 19923550 BACKGROUND

Related Links

• UCLA Longevity Center

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Curcumin; Dietary Supplements; Sugars

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Diarylheptanoids; Heptanes; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Carbohydrates

Results Point of Contact

• Title: Gary Small, MD
• Organization: University of California, Los Angeles

gsmall@mednet.ucla.edu

310-825-0291

Study Officials

• Gary W Small, MD

  UCLA Longevity Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 22, 2011
• First Posted: June 28, 2011
• Study Start: March 1, 2012
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2017
• Last Updated: March 3, 2020
• Results First Posted: March 19, 2018

Record last verified: 2020-02

Locations

US (1)