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

September 15, 2020 updated by: VA Office of Research and Development

Curcumin and Yoga Exercise Effects in Veterans at Risk for Alzheimer's Disease

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • West Los Angeles, California, United States, 90073
        • VA Greater Los Angeles Healthcare System, West Los Angeles, CA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 90 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: FACTORIAL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
0, 6, and 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
0 and 6 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
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).
0, 6, 12 months
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].
0,3,6,9,12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Investigators

  • Principal Investigator: Sally A Frautschy, PhD, VA Greater Los Angeles Healthcare System, West Los Angeles, CA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 20, 2014

Primary Completion (ACTUAL)

March 16, 2020

Study Completion (ANTICIPATED)

December 31, 2020

Study Registration Dates

First Submitted

February 11, 2013

First Submitted That Met QC Criteria

March 12, 2013

First Posted (ESTIMATE)

March 14, 2013

Study Record Updates

Last Update Posted (ACTUAL)

September 17, 2020

Last Update Submitted That Met QC Criteria

September 15, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • E0669-I
  • VA_RX00069 (OTHER_GRANT: Veterans Affairs)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Time Frame

January 1, 2020 is our deadline to published the data.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF
  • CSR

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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