Can Lifestyle Changes Reverse Early-Stage Alzheimer's Disease

• Sponsor: Preventive Medicine Research Institute (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04606420
• Collaborator: University of California, San Francisco (Other), Harvard Medical School (HMS and HSDM) (Other), University of California, San Diego (Other)
• Enrollment: 100
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 50.9
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

The objective of this study is to determine if comprehensive lifestyle changes may slow, stop, or reverse the progression of early-stage Alzheimer's disease.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease	Behavioral: Lifestyle medicine	Phase 2

Detailed Description

100 patients who have early Alzheimer's disease (MoCA above 17) in the San Francisco Bay area are being enrolled over time and are randomly assigned to one of two groups.

After baseline testing, the first group then receives this lifestyle medicine program for 20 weeks, four hours/day, three days/week (all done virtually via Zoom since March 2020 due to COVID-19).

The second group will not receive the lifestyle program for 20 weeks and will serve as a randomized control group during this phase of the study.

Both groups will be re-tested after 20 weeks.

Then, the second group will "cross over" and receive this lifestyle medicine program for 20 weeks and the first group will continue the lifestyle program for 20 additional weeks. After a total of 40 weeks, both groups will be re-tested again and compared. Those initially randomly assigned to the control group will receive the intervention for 40 weeks and then be re-tested at that time.

The intervention may be extended beyond 40 weeks.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: In this modified crossover design, 100 patients who have early Alzheimer's disease in the San Francisco Bay area are being enrolled and are randomly-assigned to one of two groups. After baseline testing, the first group then receives the lifestyle medicine program for 20 weeks, four hours/day, three days/week (all done virtually via Zoom since February 2020 due to the COVID-19 pandemic). The second group will not and will serve as a randomized control group during this phase of the study. Both groups will be re-tested after 20 weeks. Then, the second group will "cross over" and receive this lifestyle medicine program for 20 weeks and the first group will continue the lifestyle change program for 20 additional weeks. After a total of 40 weeks, both groups will be re-tested again and compared. Those patients initially randomly assigned to the control group will receive the intervention for a total of 40 weeks and then be re-tested. All patients may be tested again after two years.In this modified crossover design, 100 patients who have early Alzheimer's disease in the San Francisco Bay area are being enrolled and are randomly-assigned to one of two groups. After baseline testing, the first group then receives the lifestyle medicine program for 20 weeks, four hours/day, three days/week (all done virtually via Zoom since February 2020 due to the COVID-19 pandemic). The second group will not and will serve as a randomized control group during this phase of the study. Both groups will be re-tested after 20 weeks. Then, the second group will "cross over" and receive this lifestyle medicine program for 20 weeks and the first group will continue the lifestyle change program for 20 additional weeks. After a total of 40 weeks, both groups will be re-tested again and compared. Those patients initially randomly assigned to the control group will receive the intervention for a total of 40 weeks and then be re-tested. All patients may be tested again after two years.
• Masking: Single (Outcomes Assessor)
• Masking Description: Since this is a behavioral intervention, it is not possible to blind the participant and the care provider from whether or not they are receiving the intervention. However, everyone involved in testing patients (Outcome Assessors) is blinded to group assignment.
• Primary Purpose: Treatment
• Official Title: Lifestyle Intervention for Early Alzheimer's Disease
• Actual Study Start Date: Sep 4, 2018
• Anticipated Primary Completion Date: Nov 1, 2022
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental (Intervention) Group These patients will receive the comprehensive lifestyle medicine intervention from day 1 through the end of the study. They will be tested at baseline, after 20 weeks, and after 40 weeks. There may be subsequent testing after 2 years.	Behavioral: Lifestyle medicine; Diet: A low fat (10-15%) whole foods vegan diet, high in complex carbs and low in refined carbs (fruits, vegetables, whole grains, legumes, soy, seeds & nuts). Calories unrestricted. Multivitamin, fish oil, curcumin, vitamin C, B12, CoQ10, lion's mane, probiotic, and magnesium. 21 meals/week and supplements provided to participants and caregivers at no cost to them. Exercise: Aerobic (e.g., walking) and strength training 30 minutes/day based on a personalized prescription from an exercise physiologist or certified personal trainer and registered nurse. Stress Management: Meditation, gentle yoga-based poses, progressive relaxation, breathing exercises, and meditation (with optional glasses) 1 hour per day, supervised by a certified stress management specialist. Group Support: Participants and their spouses/caregivers participate in a support group one hour/session, 3 days/week, supervised by a licensed mental health professional in a supportive, safe environment.
No Intervention: Control (Non-Intervention) Group These patients will be asked to continue their current diet and lifestyle without making any changes for 20 weeks. They will be tested at baseline and after 20 weeks. Then, they will "cross over" and receive the same lifestyle medicine intervention for 20 weeks and will be tested again after 20 weeks of the intervention and also after 40 weeks of the intervention. There may be subsequent testing after 2 years.

Outcome Measures

Primary Outcome Measures

1. Change from Baseline in Alzheimer Disease Assessment Scale cognitive section (ADAS-Cog) score [At baseline and also after 20 weeks, 40 weeks, and 2 years]

   The ADAS-Cog test is one of the most frequently used tests to measure cognition in clinical trials. Patients obtain scores of 0 to 70; higher scores indicate poorer performance.

2. Change from Baseline in Clinical Global Impression of Change (CGIC) score [At baseline and also after 20 weeks, 40 weeks, and 2 years]

   The CGIC test is often used in clinical trials of cognition. CGIC scores range from 1 (very much improved) through to 7 (very much worse).

3. Change from Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score [At baseline and also after 20 weeks, 40 weeks, and 2 years]

   The CDR-SOB is a commonly used dementia staging instrument. The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18 (lower is better).

Secondary Outcome Measures

1. Changes from baseline in the microbiome [At baseline and also after 20 weeks, 40 weeks, and 2 years]

   This test measures the type and relative preponderance of gut organisms at Rob Knight's lab at UCSD. To assess whether this intervention is associated with a systematic signal in the gut microbiome, he will use 16S rRNA amplicon sequencing, metagenomic sequencing, and untargeted mass spectrometry to analyze stool samples of these study participants. This will provide the relative proportion of organisms in the microbiome of these patients at each time interval.

2. Changes from baseline in telomere length [At baseline and also after 20 weeks, 40 weeks, and 2 years]

   The leukocyte telomere length assay from PBMCs will be performed in the laboratory of Dr. Elizabeth Blackburn at UCSF using the quantitative polymerase chain reaction method to measure telomere length relative to standard reference DNA, expressed as telomere to single-copy gene ratio (T/S).

3. Changes from baseline in biomarkers [At baseline and also after 20 weeks, 40 weeks, and 2 years]

   These are measures of inflammation (C-reactive protein in mg/L), lipids (total cholesterol, LDL-cholesterol, triglycerides in mg/dl), blood pressure (mm Hg), and weight (pounds).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Current diagnosis of mild dementia or mild cognitive impairment due to Alzheimer's disease/process, with MoCA score above 17 (i.e., 18 or higher)

• Willingness and ability to participate in all aspects of the intervention

• Availability of spouse or caregiver who can provide collateral information and assist with study adherence

• PET scans and/or C2N testing will be performed at baseline if there is any doubt about the clinical diagnosis of Alzheimer's disease

Exclusion Criteria:

• severe dementia

• physical disability that precludes regular exercise

• clear evidence for other causes of neurodegeneration or dementia, e.g., severe cerebrovascular disease, Parkinson's disease

• significant ongoing psychiatric or substance abuse problems

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dean Ornish, M.D.	Sausalito	California	United States	94965

Sponsors and Collaborators

• Preventive Medicine Research Institute
• University of California, San Francisco
• Harvard Medical School (HMS and HSDM)
• University of California, San Diego

Investigators

• Principal Investigator: Dean Ornish, MD, President, Preventive Med Res Inst; Clinical Prof Medicine UCSF
• Study Director: Catherine Madison, MD, Chief Neurologist, Preventive Medicine Research Institute
• Principal Investigator: Kim Norman, MD, PI at UCSF & Distinguished Professor of Psychiatry

Study Documents (Full-Text)

None provided.

More Information

Publications

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• Responsible Party: Preventive Medicine Research Institute
• ClinicalTrials.gov Identifier: NCT04606420
• Other Study ID Numbers: 20172897
• First Posted: Oct 28, 2020
• Last Update Posted: Oct 28, 2020
• Last Verified: Oct 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Preventive Medicine Research Institute: Mild Cognitive Impairment
• Additional relevant MeSH terms: Alzheimer Disease

Study Results

No Results Posted as of Oct 28, 2020