Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Walnuts and Healthy Aging (WAHA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01634841
Recruitment Status : Completed
First Posted : July 6, 2012
Last Update Posted : June 24, 2021
Sponsor:
Collaborators:
University of Barcelona
California Walnut Commission
Information provided by (Responsible Party):
Joan Sabate,DrPH, MD, Loma Linda University

Tracking Information
First Submitted Date  ICMJE June 20, 2012
First Posted Date  ICMJE July 6, 2012
Last Update Posted Date June 24, 2021
Study Start Date  ICMJE April 2012
Actual Primary Completion Date May 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 19, 2019)
  • Changes from baseline in global cognitive composite score [ Time Frame: 2 years ]
    The composite score will be calculated using the scores from the tests listed below. We will calculate the standardized scores of each test as the score of each participant minus the group mean and divide by its standard deviation. The composite score is the mean of the standardized scores. The 12 tests are: Rey Auditory Verbal Learning Test (RAVLT), Rey-Osterrieth Complex Figure (ROCF), Semantic Fluency (Animals), Boston Naming Test (BNT), Visual Object and Space Perception Battery (VOSP), Block Design section from the Wechsler Adult Intelligence Scale (WAIS-III), Trail Making Test (TMT), FAS Word Fluency, Stroop Color Word Test, Symbol Digit Modalities Test (SMDT) Digit Span from the WAIS-III and Conners Continuous Performance Test (CPT-II).
  • Changes from baseline in macular degeneration [ Time Frame: 2 years ]
    This will be assessed: by stereoscopic digitized color fundus images graded by International Classification System for Age-Related Maculopathy (score range. 0 to 4; the higher the score, the worse the condition); by optical coherence tomography (OCT) measurements of macular thickness (in µm); by optical coherence tomography (OCT) measurements of retinal nervous fiber layer thickness (in µm).
Original Primary Outcome Measures  ICMJE
 (submitted: July 5, 2012)
% Change in cognitive decline from baseline [ Time Frame: 2 years ]
Baseline data will be collected using the following neuropsychological evaluations: MMSE, NART, WAIS III tests of intelligence; ROCF, RAVLT for memory; BNT and semantic category evocation for language; VOSP for perception; copy ROCF for praxis; TMT A, TMT B, FAS word fluency, Stroop test, SDMT, CPT II, CANTAB for frontal cognition. From baseline we hypothesize there will be a 5% difference in cognitive decline between the walnut intervention group and the control group when tests are performed again after the 2 year intervention.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2019)
  • Change from baseline in brain cortical thickness [ Time Frame: 2 years ]
    Changes will be assessed by brain magnetic resonance imaging (MRI) on a randomly selected subset of participants. Only in Barcelona center. Unit of measure is mm2.
  • Change from baseline in voxel-based morphometry [ Time Frame: 2 years ]
    Changes will be assessed by brain magnetic resonance imaging (MRI) using GM density maps on a randomly selected subset of participants. Only in Barcelona center. Unit of measure is GM density.
  • Change from baseline in white matter hyperintensity volumes [ Time Frame: 2 years ]
    Changes will be assessed by brain magnetic resonance imaging (MRI) on a randomly selected subset of participants. Only in Barcelona center. Unit of measure is mL.
  • Change from baseline in perfusion arterial spin labeling [ Time Frame: 2 years ]
    Changes will be assessed by brain magnetic resonance imaging (MRI) on a randomly selected subset of participants. Only in Barcelona center. Unit of measure is ml/100 g/min.
  • Changes from baseline in brain activation [ Time Frame: 2 years ]
    Changes will be assessed by Functional MRI (fMRI) on a randomly selected subset of participants. Only in Barcelona center. There are no units of measure.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 5, 2012)
% change in macular degeneration from baseline [ Time Frame: 2 years ]
We hypothesize that 30 to 45g per day of walnuts will delay the onset and progression of macular degeneration in healthy elderly subjects. This will be determined by a difference of 5% in the thickness of the retina as measured by OCT.
Current Other Pre-specified Outcome Measures
 (submitted: September 19, 2019)
  • Change in carotid Intima-media thickness (mm) [ Time Frame: 2 years ]
    Changes will be assessed by high-resolution ultrasound. Only in Barcelona center.
  • Incidence of plaque presence in carotid artery (yes/no) [ Time Frame: 2 years ]
    Changes will be assessed by high-resolution ultrasound. Only in Barcelona center.
  • Change in carotid atheroma plaque height (mm) [ Time Frame: 2 years ]
    Changes will be assessed by high-resolution ultrasound. Only in Barcelona center.
  • Change in body mass index (kg/m2) [ Time Frame: 2 years ]
    BMI will be calculated as weight in kilograms divided by height in metres squared
  • Change in waist circumference (cm) [ Time Frame: 2 years ]
    Waist circumference will be measured to the nearest 0.5 cm by using an anthropometric tape midway between the lowest rib and at the iliac crest at minimal respiration
  • Change in total fat (g) [ Time Frame: 2 years ]
    Changes will be assessed by Dual-energy X-ray absorptiometry. Only in Barcelona center.
  • Change in Total lean tissue (g) [ Time Frame: 2 years ]
    Changes will be assessed by Dual-energy X-ray absorptiometry. Only in Barcelona center.
  • Change in fasting serum total cholesterol (mg/dL) [ Time Frame: 2 years ]
    Fasting serum total cholesterol will be measured by a standard enzymatic method
  • Change in fasting serum LDL-cholesterol (mg/dL) [ Time Frame: 2 years ]
    Fasting serum LDL-cholesterol will be estimated by the Friedewald formula
  • Change in fasting serum HDL-cholesterol (mg/dL) [ Time Frame: 2 years ]
    Fasting serum HDL-cholesterol will be measured by a precipitation technique
  • Change in fasting serum triglycerides (mg/dL) [ Time Frame: 2 years ]
    Fasting triglycerides will be measured by a standard enzymatic method
  • Change in serum brain-derived neurotrophic factor (pg/mL) [ Time Frame: 2 years ]
    Assessed by ELISA
  • Change in serum soluble-Selectin (ng/mL) [ Time Frame: 2 years ]
    Assessed by ELISA
  • Change in serum soluble-intercellular Adhesion Molecule 1 (ng/mL) [ Time Frame: 2 years ]
    Assessed by ELISA
  • Change in serum soluble-vascular cell adhesion molecule 1 (ng/mL) [ Time Frame: 2 years ]
    Assessed by ELISA
  • Change in serum amyloid A (ng/mL) [ Time Frame: 2 years ]
    Assessed by ELISA
  • Change in serum granulocyte-macrophage colony-stimulating factor (pg/mL) [ Time Frame: 2 years ]
    Assessed by ELISA
  • Change in serum interferon-gamma (pg/mL) [ Time Frame: 2 years ]
    Assessed by ELISA
  • Change in serum interleukin-1beta (pg/mL) [ Time Frame: 2 years ]
    Assessed by ELISA
  • Change in serum interleukin-6 (pg/mL) [ Time Frame: 2 years ]
    Assessed by ELISA
  • Change in serum tumor necrosis factor alpha (pg/mL) [ Time Frame: 2 years ]
    Assessed by ELISA
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Walnuts and Healthy Aging
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Prevention
Condition  ICMJE
  • Age Related Cognitive Decline
  • Age Related Macular Degeneration
Intervention  ICMJE
  • Dietary Supplement: Walnuts
    30 to 60g (1 to 2 oz) per day of walnuts
  • Other: habitual diet
    Dietary information will be provided
Study Arms  ICMJE
  • Active Comparator: Walnut group
    This group will have their habitual diet supplemented with 30 to 45g (1 to 1.5 oz) of walnuts daily.
    Intervention: Dietary Supplement: Walnuts
  • Active Comparator: Control group
    This group will eat their habitual diet and refrain from eating walnuts.
    Intervention: Other: habitual diet
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 16, 2016)
708
Original Estimated Enrollment  ICMJE
 (submitted: July 5, 2012)
700
Actual Study Completion Date  ICMJE May 2016
Actual Primary Completion Date May 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 63 Years to 79 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01634841
Other Study ID Numbers  ICMJE 5120066
670715-3833 ( Other Identifier: Loma Linda University )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Joan Sabate,DrPH, MD, Loma Linda University
Study Sponsor  ICMJE Loma Linda University
Collaborators  ICMJE
  • University of Barcelona
  • California Walnut Commission
Investigators  ICMJE
Principal Investigator: Joan Sabate, MD, DrPH Chair, Department of Nutrition
Principal Investigator: Emilio Ros, MD, PhD Director Lipid Clinic, Endocrinology & Nutrition Service
PRS Account Loma Linda University
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP