The PROtein Enriched MEDiterranean Diet and EXercise Trial for Older Adults at Risk of Undernutrition (PROMED-EX)

A Randomised Controlled Trial to Evaluate the Effect of a Protein Enriched Mediterranean Diet and Exercise Intervention on the Nutritional Status and Cognitive Performance of Adults at Risk of Undernutrition and Cognitive Decline

PROMED-EX is a single-blind, parallel group randomised controlled trial to determine the effect of a PROtein enriched MEDiterranean diet (PROMED) in comparison to a PROtein enriched MEDiterranean diet and EXercise (PROMED-EX) intervention, or standard care on the nutritional status and cognitive performance of older undernourished adults with subjective cognitive decline.

Study Overview

• Status: Recruiting
• Conditions: Cognitive Impairment; Cognitive Decline; Poor Nutrition
• Intervention / Treatment: Behavioral: A Protein Enriched Mediterranean Diet (PROMED) Intervention; Behavioral: A Protein Enriched Mediterranean Diet & Exercise (PROMED-EX) Intervention

Detailed Description

Undernutrition is common in older adults and can cause significant negative impacts on the health of older people, leading to weight loss and decline in cognitive function (memory and thinking abilities), loss of independence and hospitalisation. Undernutrition is associated with £23.5 billion/year in health and social care costs in the United Kingdom - over half of these costs are related to undernutrition in older adults.

Research suggests that undernutrition and weight loss occur a long time (at least 10 years) before the symptoms of cognitive decline become apparent. This means that correcting undernutrition and weight loss could help to prevent the onset of cognitive impairment.

The aim of the PROMED-EX trial is to test the effect of a 6-month protein enriched Mediterranean diet, with and without exercise, on the risk of undernutrition and cognitive decline in older adults in Northern Ireland. The PROMED-EX trial will recruit 105 older adults living in the community, at risk of poor nutrition, with a decline in memory but without a diagnosed cognitive impairment. Investigators will collect several measurements to determine the nutritional status and cognitive functioning of study participants and will repeat measurements during the study (at the start of the study, at 3 months (study midpoint) and at 6 months (study endpoint).

The goal is to identify potential effective solutions to undernutrition which can reduce cognitive decline and other negative health impacts on older adults. The research can be used to guide public health dietary guidelines for older people to prevent undernutrition and increase healthy life years.

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Claire McEvoy, PhD; Phone Number: +44 (0)28 9097 6078; Email: c.mcevoy@qub.ac.uk

Study Locations

• United Kingdom
  • Antrim
    • Belfast, Antrim, United Kingdom, BT12 6BJ
      • Recruiting
      • Queen's University Belfast
      • Contact: Claire McEvoy, PhD; Phone Number: +44 (0)28 9097 6078; Email: c.mcevoy@qub.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Community-dwelling (non-institutionalised) participants ≥60 years older
• A high risk of undernutrition as defined by a Mini Nutritional Assessment -Short Form (MNA-SF) score of 8 - 11
• Positive screen for Subjective Cognitive Decline (SCD)

Exclusion Criteria:

• Cognitive impairment determined by the Mini Mental State Assessment (MMSE) or Telephone Cognitive Screen (T-CogS)
• Receiving oral or artificial nutritional support or medical food supplements
• Taking high dose nutritional supplements (supplements above the Reference Nutrient Intake levels).
• Dietary restrictions/allergies that limit ability to adhere to study requirements
• A diagnosis of mild cognitive impairment or dementia
• Dysphagia
• Chronic kidney disease
• Poorly controlled diabetes (HbA1c >8% or diabetes complications)
• Severe visual or language impairment
• Self-reported psychiatric problems or significant medical co-morbidities that compromise the ability to take part/limit capacity to consent
• Diagnosis of a comorbid condition that may alter performance on cognitive tests, e.g. stroke, head injury, Parkinson's disease, learning disabilities.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PROMED (Experimental Intervention 1); A Protein Enriched Mediterranean Diet (PROMED) intervention. Participants will receive individually tailored resources to encourage adoption of a protein-enriched Mediterranean diet pattern.	Behavioral: A Protein Enriched Mediterranean Diet (PROMED) Intervention; Researchers will provide individually tailored dietary advice and written materials to encourage 'a little and often' meal plan to support adoption of the PROMED intervention. The daily energy and protein requirements of each participant will be calculated based on National Institute of Health & Care Excellence guidance for Nutrition Support in Adults at Risk of Malnutrition. Several resources have been developed to facilitate behaviour change: a) A PROMED Diet Information Booklet to include an overview of the PROMED Diet, tips for incorporating more PROMED foods into the diet and information on the health benefits of a PROMED diet, b) A PROMED Recipe Book offering ideas for breakfast, lunch and dinner as well as suitable snack ideas and c) key PROMED foods ordered through a local supermarket's online delivery service and delivered to participants' homes on a weekly or fortnightly basis for the 3-month active intervention phase.
Experimental: PROMED-EX (Experimental Intervention 2); A Protein Enriched Mediterranean Diet & Exercise (PROMED-EX) Intervention. Participants will receive the same PROMED diet resources (Experimental Intervention 1) and an individually tailored exercise intervention.	Behavioral: A Protein Enriched Mediterranean Diet & Exercise (PROMED-EX) Intervention; Participants will receive a dietary intervention identical to PROMED participants, plus an exercise intervention. The home-based exercises are based on a modified version of the 'ExWell@home' programme developed by health professionals with significant expertise in community-based exercise rehabilitation for chronic disease. Cardiorespiratory fitness will be determined using a 3-minute step test and pulse rate. Participants will receive access to pre-recorded exercise classes and a written resource designed for older adults (ExWell@home) and adapted for the current study. Participants will be encouraged to complete two sessions per week (30-60 minutes per session). To cater for differing abilities, four levels of classes will be available for participants: Chair based, basic, standard and advanced.
No Intervention: Control group; 'Standard Care' - consisting of a general diet information sheet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini Nutritional Assessment Score- Long Form	The Primary outcome is change at 6 months (study endpoint) in Mini Nutritional Assessment (MNA) score between the two intervention groups and the control group. The MNA is a well validated tool with good sensitivity and specificity for predicting nutritional risk in older community dwelling adults. Scores range from 0-30 with a lower score reflecting poorer nutritional status.	Baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini Nutritional Assessment Score (midpoint change)	Change at 3 months from baseline in Mini Nutritional Assessment (MNA) score between the two intervention groups and the control group. The MNA is a well validated tool with good sensitivity and specificity for predicting nutritional risk in older community dwelling adults. Scores range from 0-30 with a lower score reflecting poorer nutritional status.	Baseline and 3 months
Weight (kg) and height (cm)	Change in weight (kg) and Height (cm) at 3 and 6 months (from baseline). Both measurements will be used to calculate change in Body Mass Index (BMI) (Kg/m^2) across groups at 3 and 6 months.	Baseline, 3 months and 6 months
Total Body Fat (%)	Change in Total Body Fat (%) at 3 and 6 months (from baseline) using Bioelectrical Impedance Analysis (BodyStat 1500)	Baseline, 3 months and 6 months
Systolic Blood Pressure (mmHg)	Change at 3 and 6 months (from baseline) using a Omron automated blood pressure monitor	Baseline, 3 months and 6 months
Diastolic Blood Pressure (mmHg)	Change at 3 and 6 months (from baseline) using an Omron automated blood pressure monitor	Baseline, 3 months and 6 months
Capturing Changes in Cognition (Catch-Cog)	Change at 3 and 6 months (from baseline) in cognition using the Capturing Changes in Cognition- Catch-Cog score. This composite includes an Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) word recognition (Sub score 0-12), ADAS-Cog orientation (Sub score 0-8), Controlled Oral Word Association Test (COWAT) (max number of words in 1 minute), Category Fluency Test (max number of words in 1 minute), a Digital Symbol Substitution test (correct number of symbols matched in 90 seconds), and an ADAS-Cog Word Recall Test (sub score range: 0-10). A higher score reflects better cognitive performance.	Baseline, 3 months and 6 months
Trail Making Tests (TMT) (Part A & B)	Change in completion time of the TMT at 3 and 6 months (from baseline). Higher time reflects greater impairment.	Baseline, 3 months and 6 months
Simplified Nutrition Appetite Questionnaire (SNAQ)	Change in appetite at 3 and 6 months (from baseline). This is a brief 4-item questionnaire (score range 0-4) with lower scores suggesting deterioration of appetite.	Baseline, 3 months and 6 months
Geriatric Depression Scale	Change in Depression scale at 3 and 6 months (from baseline) Scores range from 0-15. A score ≥5 indicates probable depression	Baseline, 3 months and 6 months
Health-related quality of life (Short Form (SF)-36)	Change in health related quality of life measures at 3 and 6 months between the two intervention groups and control. The SF-36 is a 36-item questionnaire (covering 8 domains of health including physical functioning; role limitations due to physical health; role limitation due to emotional problems; energy/fatigue; emotional well-being; social functioning; pain; general health.Scores range from 0-100 with higher score indicating a better quality of life.	Baseline, 3 months and 6 months
Physical Activity determined by completion of a Recent Physical Activity Questionnaire	Change at 3 and 6 months (from Baseline) in physical activity levels between the two intervention groups and control. This questionnaire inquires about physical activity across four domains (leisure time, occupation, commuting, and domestic life) during the past 4 weeks. Metabolic Equivalent of Task scores can be calculated and an estimation of total energy expenditure across the four domains.	Baseline, 3 months and 6 months
Grip Strength measured by isometric grip force (0-100kg)	Change in isometric grip force (0-100kg) at 3 and 6 months (from baseline) using a Dynamometer	Baseline, 3 months and 6 months
Functional performance measured using the Short Physical Performance Battery (SPPB) test.	Change at 3 and 6 months in functional performance from baseline (using the SBBP): The SPPB will test participant's Gait (time to walk 8 feet), Balance (ability to complete a side-by-side, a semi-tandem and a tandem stand) and Strength (time to complete 5 chair stands). Category scores range from 0-4 and total score (0-12) with a higher score representing better physical functioning.	Baseline, 3 months and 6 months
Lean Muscle Mass (kg)	Change in Muscle Mass (kg) at 3 and 6 months (from baseline) using Bioelectrical Impedance Analysis (BodyStat 1500)	Baseline, 3 months and 6 months
Nutrient intake: PROMED Mediterranean Diet Score	Change at 3 and 6 months in Mediterranean Diet Score (MDS)(score range 0-14) between the two intervention groups and control. Higher scores reflect greater adherence to a Mediterranean diet.	Baseline, 3 months and 6 months
Nutrient intake: (4 day food diary)	Change at 3 and 6 months in nutrient intakes (including protein intake) between the two intervention groups and control.	Baseline, 3 months and 6 months
Body Water (%)	Change in Body water (%) at 3 and 6 months (from baseline) using Bioelectrical Impedance Analysis (BodyStat 1500)	Baseline, 3 months and 6 months
Waist circumference (cm)	Change in waist circumference at 3 and 6 months (from baseline)	Baseline, 3 months and 6 months
Delayed recall test (0-10)	Change at 3 and 6 months (from baseline) in a delayed recall test of recalled learned words after a 5-minute delay (score range 0-10)	Baseline, 3 months and 6 months
Biochemical markers: nutritional, cardiometabolic and inflammatory	Blood sample will be collected to determine change in serum levels of Vitamin A, Vitamin E , Carotenoids (nmol/l), change in serum lipid profile (Total cholesterol, HDL cholesterol, LDL Cholesterol and triglycerides (mmol/l)), HbA1c (mmol/mol) , fasting plasma glucose (mmol/l) and Insulin (pmol/l), High Sensitivity C-Reactive Protein (mg/l), Interleukin-6 (pg/ml),at 3 and 6 months (from Baseline).	Baseline, 3 months and 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Explore the acceptability and tolerance of the intervention	A study evaluation questionnaire will be administered to participants at 6 months to determine acceptability, tolerance and potential adverse effects of the intervention components and the intervention materials	6 months
Exploratory outcome: Metabolomic profiling	The blood samples required for Metabolomics analysis will be transferred to University College Dublin. An exploratory outcome using both targeted and untargeted approaches. Metabolomics will be performed using NMR and LC-MS-based approaches.	Baseline, 3 months and 6 months

Collaborators and Investigators

• Sponsor: Queen's University, Belfast
• Collaborators: University College Dublin; Wageningen University; Dublin City University; Friedrich-Alexander-Universität Erlangen-Nürnberg
• Investigators: Principal Investigator: Claire McEvoy, PhD, Queen's University, Belfast

Publications and helpful links

Helpful Links

• Link to PROMED-COG consortium and trial website

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2022
• Primary Completion (Estimated): January 31, 2024
• Study Completion (Estimated): January 31, 2024

Study Registration Dates

• First Submitted: September 17, 2021
• First Submitted That Met QC Criteria: December 8, 2021
• First Posted (Actual): December 22, 2021

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Cognitive decline; Cognitive impairment; Older adults; Mediterranean Diet; Poor nutrition; Protein enriched Mediterranean Diet
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Nutrition Disorders; Cognition Disorders; Cognitive Dysfunction; Malnutrition
• Other Study ID Numbers: B21/16; BB/V019201/1 (Other Grant/Funding Number: UK Research & Innovation (UKRI):BBSRC MRC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be deposited in free open access repositories e.g. Queen's University Belfast (QUB) Pure Research portal and Zenodo (https://zenodo.org/), with guaranteed preservation of for ten years or more in order to maximise discovery and data sharing opportunities. The study description and variable metadata catalogues will be published also. Where possible, metadata will be made available through the Joint Programme Initiative: a Healthy Diet for a Healthy Life (JPI-HDHL) Meta Database (http://www.jpihdhl.eu) to maximise the visibility to the wider research community.
• IPD Sharing Time Frame: Data will be made available once statistical analyses have been complete and for 10 years thereafter.

IPD Sharing Access Criteria

The following conditions will apply to data use:

• agreement on methodology
• allowance to link the dataset with other datasets
• data security
• agreement on publication and authorship

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No