Clinical trial NCT01634841: Walnuts and Healthy Aging
Official title: Effect of Daily Ingestion of Walnuts for 2 Years on Age-related Cognitive Decline and Macular Degeneration in Healthy Elderly Subjects: A Randomized, Single Blind, Dual Center, Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Age Related Cognitive Decline
Age Related Macular Degeneration
Keywords: walnuts
age related cognitive decline
age related macular degeneration
healthy elderly subjects
Lead sponsor: Loma Linda University
Sponsor class: OTHER
Collaborators: name: University of Barcelona
name: California Walnut Commission
First posted: 2012-07-06
Enrollment: 708
Sex: ALL
Minimum age (years): 63
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This will be a systematic investigation of the role of walnuts in preventing or slowing age related cognitive decline and age related macular degeneration. 700 subjects will be recruited between 2 sites, Loma Linda University in California, USA and Hospital Clinic in Barcelona, Spain. Participants will be randomly assigned to either the walnut group or the control group for a 2 year intervention. Baseline and annual data will be collected and analyzed.

Detailed description: Epidemiological studies suggest that nutrients such as n-3 polyunsaturated fatty acid, antioxidants and B-vitamins may protect against age related cognitive decline. Small human studies have shown beneficial effects of polyphenol rich foods on cognition and age related macular degeneration. Walnuts are a rich source of n-3 polyunsaturated fatty acid, alpha-linolenic acid, antioxidants, polyphenols and other bioactive compounds. A 2-year intervention will be conducted with healthy, elderly subjects to investigate the role of walnuts in preventing or slowing age related cognitive decline and age related macular degeneration.

350 subjects, age 63 to 79 years, will be recruited at each of 2 sites, Loma Linda University in California and Hospital Clinic in Barcelona. Participants will be randomly assigned to one of two groups: walnut group (habitual diet with 1 or 2 oz/d walnut supplement) or control group (habitual diet only). At baseline and yearly, cardiometabolic risk factors, red blood cell membrane fatty acids, urinary polyphenols and biomarkers of inflammation and oxidation will be measured. Eye exam, blood pressure and cognitive function tests will be measured at the beginning and end of 2 years. At the Barcelona site only, participants will be given a brain MRI and carotid ultrasound.

Descriptive results will be reported as mean plus/minus standard deviation. Primary analysis will be carried out on the basis of groups as randomly assigned. Results will be presented as appropriate effect sizes with a measure of precision (95% CI). Analysis of covariates gender, age, educational status will be conducted.

Eligibility criteria: Inclusion Criteria:

* 63 to 79 years old
* healthy men and women
* able to attend clinic at a study sites

Exclusion Criteria:

* illiteracy or inability to understand the protocol
* unable to undergo neurophysiological tests
* morbid obesity (BMI greater than or equal to ≥ 40 kg/m2)
* uncontrolled diabetes (HbA1c\>85)
* uncontrolled hypertension
* prior cerebrovascular accident
* any relevant psychiatric illness, including major depression
* advanced cognitive deterioration, dementia
* other neurodegenerative diseases (i.e. Parkinson's disease)
* any chronic illness expected to shorten survival (heart, liver, cancer, etc)
* bereavement in the first year of loss
* bad dentures unless fixable dental prostheses are used
* allergy to walnuts
* customary us of fish oil or flaxseed oil supplements
* eye related exclusion criteria

Primary outcomes:
measure: Changes from baseline in global cognitive composite score
timeFrame: 2 years
measure: Changes from baseline in macular degeneration
timeFrame: 2 years
Secondary outcomes:
measure: Change from baseline in brain cortical thickness
timeFrame: 2 years
measure: Change from baseline in voxel-based morphometry
timeFrame: 2 years
measure: Change from baseline in white matter hyperintensity volumes
timeFrame: 2 years
measure: Change from baseline in perfusion arterial spin labeling
timeFrame: 2 years
measure: Changes from baseline in brain activation
timeFrame: 2 years
Other outcomes:
measure: Change in carotid Intima-media thickness (mm)
timeFrame: 2 years
measure: Incidence of plaque presence in carotid artery (yes/no)
timeFrame: 2 years
measure: Change in carotid atheroma plaque height (mm)
timeFrame: 2 years
measure: Change in body mass index (kg/m2)
timeFrame: 2 years
measure: Change in waist circumference (cm)
timeFrame: 2 years
measure: Change in total fat (g)
timeFrame: 2 years
measure: Change in Total lean tissue (g)
timeFrame: 2 years
measure: Change in fasting serum total cholesterol (mg/dL)
timeFrame: 2 years
measure: Change in fasting serum LDL-cholesterol (mg/dL)
timeFrame: 2 years
measure: Change in fasting serum HDL-cholesterol (mg/dL)
timeFrame: 2 years
measure: Change in fasting serum triglycerides (mg/dL)
timeFrame: 2 years
measure: Change in serum brain-derived neurotrophic factor (pg/mL)
timeFrame: 2 years
measure: Change in serum soluble-Selectin (ng/mL)
timeFrame: 2 years
measure: Change in serum soluble-intercellular Adhesion Molecule 1 (ng/mL)
timeFrame: 2 years
measure: Change in serum soluble-vascular cell adhesion molecule 1 (ng/mL)
timeFrame: 2 years
measure: Change in serum amyloid A (ng/mL)
timeFrame: 2 years
measure: Change in serum granulocyte-macrophage colony-stimulating factor (pg/mL)
timeFrame: 2 years
measure: Change in serum interferon-gamma (pg/mL)
timeFrame: 2 years
measure: Change in serum interleukin-1beta (pg/mL)
timeFrame: 2 years
measure: Change in serum interleukin-6 (pg/mL)
timeFrame: 2 years
measure: Change in serum tumor necrosis factor alpha (pg/mL)
timeFrame: 2 years
Locations:
city: Loma Linda
country: United States
facility: Loma Linda University, Department of Nutrition
state: California
city: Barcelona
country: Spain
facility: Hospital Clinic, University of Barcelona
Study officials:
affiliation: Chair, Department of Nutrition
name: Joan Sabate, MD, DrPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Director Lipid Clinic, Endocrinology & Nutrition Service
name: Emilio Ros, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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