NCT01634841

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
708

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Apr 2012

Longer than P75 for not_applicable

Geographic Reach
2 countries

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2012

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

June 20, 2012

Completed
16 days until next milestone

First Posted

Study publicly available on registry

July 6, 2012

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2016

Completed
Last Updated

June 24, 2021

Status Verified

June 1, 2021

Enrollment Period

4.1 years

First QC Date

June 20, 2012

Last Update Submit

June 21, 2021

Conditions

Age Related Cognitive DeclineAge Related Macular Degeneration

Keywords

walnutsage related cognitive declineage related macular degenerationhealthy elderly subjects

Outcome Measures

Primary Outcomes (2)

  • Changes from baseline in global cognitive composite score

    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).

    2 years

  • Changes from baseline in macular degeneration

    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).

    2 years

Secondary Outcomes (5)

  • Change from baseline in brain cortical thickness

    2 years

  • Change from baseline in voxel-based morphometry

    2 years

  • Change from baseline in white matter hyperintensity volumes

    2 years

  • Change from baseline in perfusion arterial spin labeling

    2 years

  • Changes from baseline in brain activation

    2 years

Other Outcomes (21)

  • Change in carotid Intima-media thickness (mm)

    2 years

  • Incidence of plaque presence in carotid artery (yes/no)

    2 years

  • Change in carotid atheroma plaque height (mm)

    2 years

  • +18 more other outcomes

Study Arms (2)

Walnut group

ACTIVE COMPARATOR

This group will have their habitual diet supplemented with 30 to 45g (1 to 1.5 oz) of walnuts daily.

Dietary Supplement: Walnuts

Control group

ACTIVE COMPARATOR

This group will eat their habitual diet and refrain from eating walnuts.

Other: habitual diet

Interventions

WalnutsDIETARY_SUPPLEMENT

30 to 60g (1 to 2 oz) per day of walnuts

Walnut group
habitual dietOTHER

Dietary information will be provided

Control group

Eligibility Criteria

Age63 Years - 79 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Loma Linda University, Department of Nutrition

Loma Linda, California, 92350, United States

Location

Hospital Clinic, University of Barcelona

Barcelona, 08036, Spain

Location

Related Publications (14)

  • Cofan M, Checa A, Serra-Mir M, Roth I, Valls-Pedret C, Lopez-Illamola A, Domenech M, Rajaram S, Lazaro I, Sabate J, Ros E, Wheelock CE, Sala-Vila A. A Walnut-Enriched Diet for 2 Years Changes the Serum Oxylipin Profile in Healthy Older Persons. J Nutr. 2024 Feb;154(2):395-402. doi: 10.1016/j.tjnut.2023.12.007. Epub 2023 Dec 9.

    PMID: 38081585DERIVED

  • Fjell AM, Sorensen O, Wang Y, Amlien IK, Baare WFC, Bartres-Faz D, Boraxbekk CJ, Brandmaier AM, Demuth I, Drevon CA, Ebmeier KP, Ghisletta P, Kievit R, Kuhn S, Madsen KS, Nyberg L, Sole-Padulles C, Vidal-Pineiro D, Wagner G, Watne LO, Walhovd KB. Is Short Sleep Bad for the Brain? Brain Structure and Cognitive Function in Short Sleepers. J Neurosci. 2023 Jul 12;43(28):5241-5250. doi: 10.1523/JNEUROSCI.2330-22.2023. Epub 2023 Jun 26.

    PMID: 37365003DERIVED

  • Nyberg L, Magnussen F, Lundquist A, Baare W, Bartres-Faz D, Bertram L, Boraxbekk CJ, Brandmaier AM, Drevon CA, Ebmeier K, Ghisletta P, Henson RN, Junque C, Kievit R, Kleemeyer M, Knights E, Kuhn S, Lindenberger U, Penninx BWJH, Pudas S, Sorensen O, Vaque-Alcazar L, Walhovd KB, Fjell AM. Educational attainment does not influence brain aging. Proc Natl Acad Sci U S A. 2021 May 4;118(18):e2101644118. doi: 10.1073/pnas.2101644118.

    PMID: 33903255DERIVED

  • Fjell AM, Sorensen O, Amlien IK, Bartres-Faz D, Brandmaier AM, Buchmann N, Demuth I, Drevon CA, Duzel S, Ebmeier KP, Ghisletta P, Idland AV, Kietzmann TC, Kievit RA, Kuhn S, Lindenberger U, Magnussen F, Macia D, Mowinckel AM, Nyberg L, Sexton CE, Sole-Padulles C, Pudas S, Roe JM, Sederevicius D, Suri S, Vidal-Pineiro D, Wagner G, Watne LO, Westerhausen R, Zsoldos E, Walhovd KB. Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium. Cereb Cortex. 2021 Mar 5;31(4):1953-1969. doi: 10.1093/cercor/bhaa332.

    PMID: 33236064DERIVED

  • Sorensen O, Brandmaier AM, Macia D, Ebmeier K, Ghisletta P, Kievit RA, Mowinckel AM, Walhovd KB, Westerhausen R, Fjell A. Meta-analysis of generalized additive models in neuroimaging studies. Neuroimage. 2021 Jan 1;224:117416. doi: 10.1016/j.neuroimage.2020.117416. Epub 2020 Oct 2.

    PMID: 33017652DERIVED

  • Hooper L, Martin N, Jimoh OF, Kirk C, Foster E, Abdelhamid AS. Reduction in saturated fat intake for cardiovascular disease. Cochrane Database Syst Rev. 2020 Aug 21;8(8):CD011737. doi: 10.1002/14651858.CD011737.pub3.

    PMID: 32827219DERIVED

  • Hooper L, Martin N, Jimoh OF, Kirk C, Foster E, Abdelhamid AS. Reduction in saturated fat intake for cardiovascular disease. Cochrane Database Syst Rev. 2020 May 19;5(5):CD011737. doi: 10.1002/14651858.CD011737.pub2.

    PMID: 32428300DERIVED

  • Sala-Vila A, Valls-Pedret C, Rajaram S, Coll-Padros N, Cofan M, Serra-Mir M, Perez-Heras AM, Roth I, Freitas-Simoes TM, Domenech M, Calvo C, Lopez-Illamola A, Bitok E, Buxton NK, Huey L, Arechiga A, Oda K, Lee GJ, Corella D, Vaque-Alcazar L, Sala-Llonch R, Bartres-Faz D, Sabate J, Ros E. Effect of a 2-year diet intervention with walnuts on cognitive decline. The Walnuts And Healthy Aging (WAHA) study: a randomized controlled trial. Am J Clin Nutr. 2020 Mar 1;111(3):590-600. doi: 10.1093/ajcn/nqz328.

    PMID: 31912155DERIVED

  • Bartres-Faz D, Gonzalez-Escamilla G, Vaque-Alcazar L, Abellaneda-Perez K, Valls-Pedret C, Ros E, Grothe MJ. Characterizing the Molecular Architecture of Cortical Regions Associated with High Educational Attainment in Older Individuals. J Neurosci. 2019 Jun 5;39(23):4566-4575. doi: 10.1523/JNEUROSCI.2370-18.2019. Epub 2019 Apr 8.

    PMID: 30962275DERIVED

  • Domenech M, Serra-Mir M, Roth I, Freitas-Simoes T, Valls-Pedret C, Cofan M, Lopez A, Sala-Vila A, Calvo C, Rajaram S, Sabate J, Ros E. Effect of a Walnut Diet on Office and 24-Hour Ambulatory Blood Pressure in Elderly Individuals. Hypertension. 2019 May;73(5):1049-1057. doi: 10.1161/HYPERTENSIONAHA.118.12766.

    PMID: 30879358DERIVED

  • Freitas-Simoes TM, Cofan M, Blasco MA, Soberon N, Foronda M, Corella D, Asensio EM, Serra-Mir M, Roth I, Calvo C, Valls-Pedret C, Casaroli-Marano RP, Domenech M, Rajaram S, Sabate J, Ros E, Sala-Vila A. The red blood cell proportion of arachidonic acid relates to shorter leukocyte telomeres in Mediterranean elders: A secondary analysis of a randomized controlled trial. Clin Nutr. 2019 Apr;38(2):958-961. doi: 10.1016/j.clnu.2018.02.011. Epub 2018 Feb 17.

    PMID: 29478886DERIVED

  • Rajaram S, Valls-Pedret C, Cofan M, Sabate J, Serra-Mir M, Perez-Heras AM, Arechiga A, Casaroli-Marano RP, Alforja S, Sala-Vila A, Domenech M, Roth I, Freitas-Simoes TM, Calvo C, Lopez-Illamola A, Haddad E, Bitok E, Kazzi N, Huey L, Fan J, Ros E. The Walnuts and Healthy Aging Study (WAHA): Protocol for a Nutritional Intervention Trial with Walnuts on Brain Aging. Front Aging Neurosci. 2017 Jan 10;8:333. doi: 10.3389/fnagi.2016.00333. eCollection 2016.

    PMID: 28119602DERIVED

  • Fernandez-Cabello S, Valls-Pedret C, Schurz M, Vidal-Pineiro D, Sala-Llonch R, Bargallo N, Ros E, Bartres-Faz D. White matter hyperintensities and cognitive reserve during a working memory task: a functional magnetic resonance imaging study in cognitively normal older adults. Neurobiol Aging. 2016 Dec;48:23-33. doi: 10.1016/j.neurobiolaging.2016.08.008. Epub 2016 Aug 20.

    PMID: 27636672DERIVED

  • Vaque-Alcazar L, Sala-Llonch R, Valls-Pedret C, Vidal-Pineiro D, Fernandez-Cabello S, Bargallo N, Ros E, Bartres-Faz D. Differential age-related gray and white matter impact mediates educational influence on elders' cognition. Brain Imaging Behav. 2017 Apr;11(2):318-332. doi: 10.1007/s11682-016-9584-8.

    PMID: 27535872DERIVED

MeSH Terms

Conditions

Macular Degeneration

Condition Hierarchy (Ancestors)

Retinal DegenerationRetinal DiseasesEye Diseases

Study Officials

  • Joan Sabate, MD, DrPH

    Chair, Department of Nutrition

    PRINCIPAL INVESTIGATOR

  • Emilio Ros, MD, PhD

    Director Lipid Clinic, Endocrinology & Nutrition Service

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator, Chair, Department of Nutrition

Study Record Dates

First Submitted

June 20, 2012

First Posted

July 6, 2012

Study Start

April 1, 2012

Primary Completion

May 1, 2016

Study Completion

May 1, 2016

Last Updated

June 24, 2021

Record last verified: 2021-06

Locations

US(1)ES(1)