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

NCT01811381 | Unknown Phase 2 DMC FDA Drug

• 2 other identifiers: E0669-IVA_RX00069
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Mild Cognitive Impairment

Keywords

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

Outcome Measures

Primary Outcomes (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.

  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 Outcomes (3)

• Changes in 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) glucose metabolism neuroimaging after supplementation compared to baseline and compared to placebo

  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

  0, 6, 12 months

• Number of Participants with Adverse Events

  0,3,6,9,12 months

Study Arms (4)

Curcumin and aerobic exercise

EXPERIMENTAL

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; Behavioral: aerobic yoga

Placebo vs non-aerobic yoga

PLACEBO COMPARATOR

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; Dietary Supplement: Placebo

Placebo vs Aerobic Yoga

ACTIVE COMPARATOR

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; Dietary Supplement: Placebo

Curcumin vs non aerobic yoga

ACTIVE COMPARATOR

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; Behavioral: aerobic yoga

Interventions

Curcumin DRUG

Subjects will take 800 mg of curcumin in 4 capsules BID per day prior to meals

Also known as: Longvida Curcumin (Verdure Sciences, Indianapolis)

Curcumin and aerobic exercise; Curcumin vs non aerobic yoga

aerobic yoga BEHAVIORAL

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.

Curcumin and aerobic exercise; Curcumin vs non aerobic yoga; Placebo vs Aerobic Yoga

non aerobic yoga BEHAVIORAL

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.

Placebo vs non-aerobic yoga

Placebo DIETARY_SUPPLEMENT

Subjects will take 4 capsules x BID of placebo

Placebo vs Aerobic Yoga; Placebo vs non-aerobic yoga

Eligibility Criteria

• Age: 50 Years - 90 Years
• Gender Eligibility Details: 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.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, 90073, United States

Location

Related Publications (14)

• Begum AN, Jones MR, Lim GP, Morihara T, Kim P, Heath DD, Rock CL, Pruitt MA, Yang F, Hudspeth B, Hu S, Faull KF, Teter B, Cole GM, Frautschy SA. Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer's disease. J Pharmacol Exp Ther. 2008 Jul;326(1):196-208. doi: 10.1124/jpet.108.137455. Epub 2008 Apr 16.

  PMID: 18417733 BACKGROUND

• Frautschy SA, Cole GM. Why pleiotropic interventions are needed for Alzheimer's disease. Mol Neurobiol. 2010 Jun;41(2-3):392-409. doi: 10.1007/s12035-010-8137-1. Epub 2010 May 2.

  PMID: 20437209 BACKGROUND

• Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, Cole GM. Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiol Aging. 2001 Nov-Dec;22(6):993-1005. doi: 10.1016/s0197-4580(01)00300-1.

  PMID: 11755008 BACKGROUND

• Garcia-Alloza M, Borrelli LA, Rozkalne A, Hyman BT, Bacskai BJ. Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model. J Neurochem. 2007 Aug;102(4):1095-104. doi: 10.1111/j.1471-4159.2007.04613.x. Epub 2007 Apr 30.

  PMID: 17472706 BACKGROUND

• Geda YE, Roberts RO, Knopman DS, Christianson TJ, Pankratz VS, Ivnik RJ, Boeve BF, Tangalos EG, Petersen RC, Rocca WA. Physical exercise, aging, and mild cognitive impairment: a population-based study. Arch Neurol. 2010 Jan;67(1):80-6. doi: 10.1001/archneurol.2009.297.

  PMID: 20065133 BACKGROUND

• Gota VS, Maru GB, Soni TG, Gandhi TR, Kochar N, Agarwal MG. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J Agric Food Chem. 2010 Feb 24;58(4):2095-9. doi: 10.1021/jf9024807.

  PMID: 20092313 BACKGROUND

• Jankowsky JL, Melnikova T, Fadale DJ, Xu GM, Slunt HH, Gonzales V, Younkin LH, Younkin SG, Borchelt DR, Savonenko AV. Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer's disease. J Neurosci. 2005 May 25;25(21):5217-24. doi: 10.1523/JNEUROSCI.5080-04.2005.

  PMID: 15917461 BACKGROUND

• Lazarov O, Robinson J, Tang YP, Hairston IS, Korade-Mirnics Z, Lee VM, Hersh LB, Sapolsky RM, Mirnics K, Sisodia SS. Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice. Cell. 2005 Mar 11;120(5):701-13. doi: 10.1016/j.cell.2005.01.015.

  PMID: 15766532 BACKGROUND

• Liang KY, Mintun MA, Fagan AM, Goate AM, Bugg JM, Holtzman DM, Morris JC, Head D. Exercise and Alzheimer's disease biomarkers in cognitively normal older adults. Ann Neurol. 2010 Sep;68(3):311-8. doi: 10.1002/ana.22096.

  PMID: 20818789 BACKGROUND

• Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci. 2001 Nov 1;21(21):8370-7. doi: 10.1523/JNEUROSCI.21-21-08370.2001.

  PMID: 11606625 BACKGROUND

• Ma QL, Yang F, Rosario ER, Ubeda OJ, Beech W, Gant DJ, Chen PP, Hudspeth B, Chen C, Zhao Y, Vinters HV, Frautschy SA, Cole GM. Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin. J Neurosci. 2009 Jul 15;29(28):9078-89. doi: 10.1523/JNEUROSCI.1071-09.2009.

  PMID: 19605645 BACKGROUND

• Scarmeas N, Luchsinger JA, Brickman AM, Cosentino S, Schupf N, Xin-Tang M, Gu Y, Stern Y. Physical activity and Alzheimer disease course. Am J Geriatr Psychiatry. 2011 May;19(5):471-81. doi: 10.1097/JGP.0b013e3181eb00a9.

  PMID: 20808142 BACKGROUND

• Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005 Feb 18;280(7):5892-901. doi: 10.1074/jbc.M404751200. Epub 2004 Dec 7.

  PMID: 15590663 BACKGROUND

• Gifford KA, Liu D, Romano R 3rd, Jones RN, Jefferson AL. Development of a subjective cognitive decline questionnaire using item response theory: a pilot study. Alzheimers Dement (Amst). 2015 Dec 1;1(4):429-439. doi: 10.1016/j.dadm.2015.09.004.

  PMID: 26878034 BACKGROUND

Related Links

• Improving care of Veterans

MeSH Terms

Conditions

Cognitive Dysfunction; Motor Activity

Interventions

Curcumin

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Behavior

Intervention Hierarchy (Ancestors)

Diarylheptanoids; Heptanes; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Study Officials

• Sally A Frautschy, PhD

  VA Greater Los Angeles Healthcare System, West Los Angeles, CA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2013
• First Posted: March 14, 2013
• Study Start: January 20, 2014
• Primary Completion: March 16, 2020
• Study Completion: December 31, 2020
• Last Updated: September 17, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, 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.

Locations

US (1)