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Curcumin and Yoga Therapy for Those at Risk for Alzheimer's Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by VA Office of Research and Development
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development
ClinicalTrials.gov Identifier:
NCT01811381
First received: February 11, 2013
Last updated: July 25, 2016
Last verified: July 2016
  Purpose
Physical exercise has proven to improve memory including in the elderly. Drugs developed to stop the underlying disease processes that cause Alzheimer's disease may not improve memory on their own without efforts to stimulate brain function. One purpose of the study is to test the clinical benefits of curcumin, a safe and effective compound isolated from the turmeric root (a component of Indian curry spices), which has been found to inhibit several potential disease pathways in Alzheimer's disease. Another purpose of this study is to determine how the addition of a physical exercise program in individuals with early memory problems may affect memory function or brain imaging and blood-based markers associated with Alzheimer's disease.

Condition Intervention Phase
Mild Cognitive Impairment
Drug: Curcumin
Behavioral: aerobic yoga
Behavioral: non aerobic yoga
Dietary Supplement: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Curcumin and Yoga Exercise Effects in Veterans at Risk for Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by VA Office of Research and Development:

Primary Outcome Measures:
  • Curcumin effects (first six month period) or curcumin and aerobic yoga effects (second six month period) on the changes in the levels of blood biomarkers for Mild Cognitive Impairment relative to baseline or relative to placebo or non-aerobic yoga. [ Time Frame: 0, 6, and 12 months ] [ Designated as safety issue: No ]
    Blood samples at baseline & follow-ups are collected & analyzed for changes in biomarkers associated with MCI and/or curcumin: Clusterin, C-reactive protein, N-terminal prohormone of brain natriuretic peptide, Apolipoprotein E, beta-amyloid, vascular cell adhesion molecule protein-1, Brain derived neurotrophic factor, Interleukin-6, Interleukin-1 beta, Interleukin 1 receptor accessory protein-like 2, Tumor necrosis factor alpha, Osteopontin. The investigators will test whether supplements and/or exercise type are associated with a decrease in the biomarkers thought to be associated with MCI


Secondary Outcome Measures:
  • Changes in 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) glucose metabolism neuroimaging after supplementation compared to baseline and compared to placebo [ Time Frame: 0 and 6 months ] [ Designated as safety issue: No ]
    Functional connectivity multivariate discriminant analysis of neuroimaging changes using 18FDG-PET predicting rapid conversion to Alzheimer will be examined in subjects on supplements compared to those on placebo. Cerebral metabolism of glucose will be assessed for those receiving supplements vs. placebo and vs baseline (first six months).

  • Curcumin effects on changes in Neuropsychological parameters compared to baseline and to placebo (first six month period) and in combination with aerobic yoga, compared to baseline and to non-aerobic yoga with curcumin or aerobic yoga with supplement [ Time Frame: 0, 6, 12 months ] [ Designated as safety issue: No ]
    Cognitive changes shown to precede Alzheimer's will be assessed using a neuropsychological battery. Behavioral symptoms will be assessed with the Neuropsychiatric Inventory Questionnaire (NPI-Q). Instrumental activities of daily living will be assessed with the Functional Activities Questionnaire. Overall assessment of disease severity will be assessed with the Clinical Dementia Rating Scale Sum of Boxes. subjects on supplements compared to those on placebo. Neuropsychiatric parameters will be assessed for those receiving supplements vs baseline or vs placebo or with those performing aerobic yoga with placebo or non aerobic yoga with curcumin (second six month period).

  • Number of Participants with Adverse Events [ Time Frame: 0,3,6,9,12 months ] [ Designated as safety issue: Yes ]
    The investigators will perform routine comprehensive blood panel test to monitor safety and tolerability of Curcumin in subjects at risk for MCI by means of adverse events, vital signs and safety laboratory assessments. [ Time Frame: is at each timepoint in the study, 3, 6, 9 and 12 months].


Estimated Enrollment: 80
Study Start Date: January 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Curcumin and aerobic exercise
For the first 6 months of the study, subjects will take 800 mg of curcumin (4 capsules x BID, p.o.) before meals. From six to 12 months after the beginning of the study, subjects will take curcumin (4 capsules BID before meals, total 800 mg/day) and also participate in an aerobic yoga exercise program (Attendance at 2 classes of 1 hour duration [or 1 hr SecureVideo Live videoconference remote classes for subject who become proficient] and 2 home practices of 30 minute duration per week).
Drug: Curcumin
Subjects will take 800 mg of curcumin in 4 capsules BID per day prior to meals
Other Name: Longvida Curcumin (Verdure Sciences, Indianapolis)
Behavioral: aerobic yoga
Each week, subjects will attend two one hour aerobic yoga classes under the supervision of certified yoga instructors and complete two 30 minute aerobic yoga practice sessions at home. If proficient, subjects will take a live-video conference remote class, HIPAA approved SecureVideo classes. Modification of consent has been approved.
Placebo Comparator: Placebo vs non-aerobic yoga
For the first 6 months of the study, subjects will take Placebo (4 capsules x BID, p.o.) before meals. From six months to 12 months from the beginning of the study, subjects will take Placebo (4 capsules x BID) and participate in a weekly non-aerobic yoga program (Attendance at 2 classes of 1 hour duration or 1 hr SecureVideo Live videoconference remote classes for subject who become proficient] and 2 home practices of 30 minute duration per week).
Behavioral: non aerobic yoga

Subjects will take two non-aerobic (stretching) classes weekly as well as practice two 30 minutes yoga routines at home weekly.

Each week, subjects will attend two one hour non-aerobic yoga classes under the supervision of certified yoga instructors and complete two 30 minute non-aerobic yoga practice sessions at home.

Dietary Supplement: Placebo
Subjects will take 4 capsules x BID of placebo
Active Comparator: Placebo vs Aerobic Yoga
For the first 6 months of the study, subjects will take Placebo (4 capsules x BID, p.o.) before meals. From six months to 12 months from the beginning of the study, subjects will take Placebo (4 capsules x BID) and participate in a weekly aerobic yoga program (Attendance at 2 classes of 1 hour duration [or 1 hr SecureVideo Live videoconference remote classes for subject who become proficient] and 2 home practices of 30 minute duration per week).
Behavioral: aerobic yoga
Each week, subjects will attend two one hour aerobic yoga classes under the supervision of certified yoga instructors and complete two 30 minute aerobic yoga practice sessions at home. If proficient, subjects will take a live-video conference remote class, HIPAA approved SecureVideo classes. Modification of consent has been approved.
Dietary Supplement: Placebo
Subjects will take 4 capsules x BID of placebo
Active Comparator: Curcumin vs non aerobic yoga
For the first 6 months of the study, subjects will take 800 mg of curcumin (4 capsules x BID, p.o.) before meals. From six months to 12 months from the beginning of the study, subjects will take Curcumin (4 capsules x BID, total 800 mg/day) and participate in a weekly non-aerobic yoga program (Attendance at 2 classes of 1 hour duration [or 1 hr SecureVideo Live videoconference remote classes for subject who become proficient] and 2 home practices of 30 minute duration per week).
Drug: Curcumin
Subjects will take 800 mg of curcumin in 4 capsules BID per day prior to meals
Other Name: Longvida Curcumin (Verdure Sciences, Indianapolis)
Behavioral: aerobic yoga
Each week, subjects will attend two one hour aerobic yoga classes under the supervision of certified yoga instructors and complete two 30 minute aerobic yoga practice sessions at home. If proficient, subjects will take a live-video conference remote class, HIPAA approved SecureVideo classes. Modification of consent has been approved.

Detailed Description:
Mild cognitive impairment (MCI) often represents the earliest stages of Alzheimer's disease (AD), as individuals meeting criteria for MCI are subsequently diagnosed with AD at much higher rates than their cognitively normal elderly peers. The goal of the current study is to determine whether dietary supplementation with a novel formulation of curcumin (a component of the curry spice turmeric), which is better absorbed and more efficiently transported into the brain, can alter biological and clinical markers associated with AD risk, and to determine whether the potential beneficial effects of curcumin supplementation are synergistic with aerobic exercise. The investigators will recruit 80 elderly participants meeting criteria for MCI. Over the second 6 months of the study, the curcumin and placebo groups will be further divided into groups receiving training in either aerobic or non-aerobic yoga to determine the synergism between curcumin supplementation and aerobic exercise. The effectiveness of these interventions will be measured using plasma samples (for expression of Alzheimer-related biomarkers), and neuropsychological, functional, and behavioral assessments (i.e. clinical measures) collected at baseline, 6 months, and 12 months after initiation of treatments, with a subset of participants receiving brain imaging at baseline and 6 months. A modification was submitted to titer the study dosage two weeks prior to study start (1 capsule BID, first five days, then 2 capsules BID for five days, then 6 capsules BID for five days, then 8 capsules BID- study dosage). Over the first 6 months of the study, participants will be randomized into equal groups receiving dietary supplementation with either curcumin or placebo. Over the second 6 months of the study, participants will be further randomized into equal groups receiving dietary supplementation with either curcumin or placebo.
  Eligibility

Ages Eligible for Study:   55 Years to 90 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age between 60 and 90 years;
  • subjective cognitive complaints;
  • Mini-Mental Status Exam (MMSE) scores 24;
  • amnestic cognitive deficits (performance 1.5 standard deviation (SD) below normative means on The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) word list learning test);
  • essentially intact activities of daily living (FAQ scores < 6);
  • Sedentary (exercise < 30 minutes a day, 3 times a week);
  • ambulatory, able exercise safely without cardiovascular symptoms, and able to pass a graded treadmill test modified for the elderly;
  • able to arrange transportation to the study;
  • Willing and intellectually able to understand and to sign an informed consent and to adhere to protocol requirements;
  • community dwelling; and
  • fluent in written and spoken English
  • must screen positive for a Modified abbreviated MCI screen on phone, before coming in to clinic for extensive testing

Exclusion Criteria:

  • diagnosis of dementia,
  • concurrent substance abuse disorder,
  • psychosis or mood disorder,
  • neurological disease affecting motor or cognitive abilities (e.g. Parkinson's disease),or other significant uncontrolled medical problems,
  • cannot get up and down from floor
  • initiation of any new medications/treatment for cognitive impairment (i.e. cholinesterase inhibitor, memantine) < 6 months prior to study enrollment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01811381

Contacts
Contact: Kimberly L Panizzon, JD (310) 478-3711 ext 48329 kimberly.panizzon@va.gov
Contact: Nancy Mohler (310) 478-3711 ext 44380 nancy.mohler@va.gov

Locations
United States, California
VA Greater Los Angeles Healthcare System, West Los Angeles, CA Recruiting
West Los Angeles, California, United States, 90073
Contact: Dean T Yamaguchi, MD    310-268-4437    Dean.Yamaguchi@va.gov   
Contact: Sally A Frautschy, PhD    (310) 468-3711 ext 46499    frautsch@ucla.edu   
Sub-Investigator: Cathy Alessi, MD MD         
Sub-Investigator: David Sultzer, MD         
Sub-Investigator: Donna Ames, MD         
Sub-Investigator: Edmond H Teng, PhD MD         
Sub-Investigator: Rebecca J Melrose, PhD         
Principal Investigator: Sally A Frautschy, PhD         
Sponsors and Collaborators
VA Office of Research and Development
Investigators
Principal Investigator: Sally A Frautschy, PhD VA Greater Los Angeles Healthcare System, West Los Angeles, CA
  More Information

Additional Information:
Publications:

Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT01811381     History of Changes
Other Study ID Numbers: E0669-I  VA_RX00069 
Study First Received: February 11, 2013
Last Updated: July 25, 2016
Health Authority: United States: Federal Government
United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by VA Office of Research and Development:
Alzheimer
Prevention
mild cognitive impairment
physical exercise
synergism
curcumin
dietary supplement
anti-inflammatory
anti-tau

Additional relevant MeSH terms:
Alzheimer Disease
Curcumin
Cognition Disorders
Mild Cognitive Impairment
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 09, 2016