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

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ClinicalTrials.gov Identifier: NCT01811381
Recruitment Status : Active, not recruiting
First Posted : March 14, 2013
Last Update Posted : September 17, 2020
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Study Description
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Brief Summary:
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 succeed only with multimodal 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 or disease Intervention/treatment Phase
Mild Cognitive Impairment Drug: Curcumin Behavioral: aerobic yoga Behavioral: non aerobic yoga Dietary Supplement: Placebo Phase 2

Detailed Description:
Subjects with Mild cognitive impairment (MCI) or Subjective Cognitive Impairment (SCD) are eligible for this study. 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. Subjects with MCI are at risk of developing AD, within 6 years. Subjects with SCD may be at risk to develop MCI. The study is stratified according to whether subjects have SCD or MCI. 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. Dosage is titered up 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. Patients are stratified according to whether they have only subjective memory complaints without MCI versus those that have MCI. Over the second 6 months of the study, participants will be further randomized into equal groups receiving dietary supplementation with either curcumin or placebo.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Curcumin and Yoga Exercise Effects in Veterans at Risk for Alzheimer's Disease
Actual Study Start Date : January 20, 2014
Actual Primary Completion Date : March 16, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Curcumin

Arms and Interventions
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Arm Intervention/treatment
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.


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]
    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 :
  1. 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 ]
    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).

  2. 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 ]
    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).

  3. Number of Participants with Adverse Events [ Time Frame: 0,3,6,9,12 months ]
    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].


Eligibility Criteria
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Ages Eligible for Study:   50 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Female subjects have the same inclusion and exclusion criteria as men. Although males have increased representation in the veteran population, which is prioritized, we make efforts to recruit females through the LA times.
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age between 50 and 90 years;
  • Mini-Mental Status Exam (MMSE) scores greater than 24;
  • subjective cognitive complaints based on subjective cognitive impairment questionaire (Gifford et al. 2015) including non-amnestic or amnestic cognitive deficits MCI (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 or SCD 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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01811381


Locations
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United States, California
VA Greater Los Angeles Healthcare System, West Los Angeles, CA
West Los Angeles, California, United States, 90073
Sponsors and Collaborators
VA Office of Research and Development
Investigators
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Principal Investigator: Sally A Frautschy, PhD VA Greater Los Angeles Healthcare System, West Los Angeles, CA
More Information
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Additional Information:

Publications:

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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT01811381    
Other Study ID Numbers: E0669-I
VA_RX00069 ( Other Grant/Funding Number: Veterans Affairs )
First Posted: March 14, 2013    Key Record Dates
Last Update Posted: September 17, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: January 1, 2020 is our deadline to published the data.
Access Criteria: we will share data in a publication (biomarker data, curcumin pharmacokinetics, cognitive and neuroimaging changes). we may also provide RNAseq data on exosomes.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by VA Office of Research and Development:
Alzheimer
Prevention
mild cognitive impairment
physical exercise
synergism
curcumin
 dietary supplement
anti-inflammatory
anti-tau
subjective memory complaints without MCI
plasma-exosomes
plasm- extracellular-derived-vesicles
Additional relevant MeSH terms:
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Alzheimer Disease
Cognitive Dysfunction
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Curcumin
 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