Exogenous Ketosis During Bed Rest in Older Adults

NCT05679596 | Completed

• 1 other identifier: 427929
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this randomized, double-blind, parallel group interventional study is to evaluate the effect of ketone bodies on healthy older adults (65-85 y) during 5 days of bed rest. The main questions it aims to answer are: Does supplementation of ketone bodies prevent the typical decline in muscle protein synthesis, muscle size, muscle function, insulin sensitivity, and muscle mitochondrial function that occurs in response to bed rest? Researchers will compare ketone supplements (KET) to an energy matched control beverage (carbohydrates and fats) to see if the ketones can rescue the decline in muscle protein synthesis rates, muscle loss, muscle function, insulin sensitivity, and mitochondrial function due to 5 days of bed rest. This may positively impact the heath of older adults subjected to bed rest.

Conditions

Muscle Protein Synthesis; Muscle Atrophy; Insulin Sensitivity; Mitochondrial Function; Physical Inactivity; Cognitive Function; Muscle Strength; Functional Capacity

Keywords

Bed rest; Muscle protein synthesis; Older adults; Muscle mitochondrial function; Insulin sensitivity; Ketone bodies

Outcome Measures

Primary Outcomes (1)

• Changes in integrated fractional synthesis rate (%/d) in response to bed rest with and without ketone monoester (KET) supplementation.

  Integrative myofibrillar fractional synthesis rate will be calculated during baseline (day 0-5) and bed rest (day 5-10) phases.

  Day 0-5 and day 5-10

Secondary Outcomes (33)

• Changes in whole body insulin sensitivity in response to bed rest with and without ketone monoester (KET) supplementation.

  Day-3 and Day 10.

• Changes in whole-body lean mass (kg) in response to bed rest with and without ketone monoester (KET) supplementation

  Day-3 and Day 10.

• Changes in leg lean mass (kg) in response to bed rest with and without ketone monoester (KET) supplementation

  Day -3 and Day 10.

• Changes in quadriceps muscle volume in response to bed rest with and without ketone monoester (KET) supplementation.

  Day -3 and Day 10.

• Changes in maximal voluntary isometric contraction (N/m) of the knee extensors in response to bed rest with and without ketone monoester (KET) supplementation.

  Day -3 and Day 10.

Study Arms (2)

Exogenous ketone monoester (KET)

EXPERIMENTAL

KET will be provided at a dose of 360 mg kg-1 body mass per serving at 2 servings per day between each main meal (ΔG®; TΔS Ltd, UK, Oxford, UK).

Dietary Supplement: ketone monoester (R)-3-hydroxybutyl (R)-3- hydroxybutyrate

Energy matched control (CON)

ACTIVE COMPARATOR

CON will be provided at a dose energy matched to the KET supplement and consist of both carbohydrate (i.e., fructose) and fat (i.e., corn and canola oil 50:50 ratio). 1/3 of the supplemental energy will come from carbohydrate while 2/3 will come from fat. We have excluded protein from the CON supplement since it is well established to influence our primary outcome measure (MPS rates). A non-caloric sweetener will also be added to the CON supplement.

Dietary Supplement: carbohydrate-fat placebo (fructose, corn and canola oil 50:50 ratio)

Interventions

ketone monoester (R)-3-hydroxybutyl (R)-3- hydroxybutyrate DIETARY_SUPPLEMENT

Provided twice a day between meals.

Also known as: delta G Oxford Ketone Ester

Exogenous ketone monoester (KET)

carbohydrate-fat placebo (fructose, corn and canola oil 50:50 ratio) DIETARY_SUPPLEMENT

Provided twice a day between meals.

Energy matched control (CON)

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Healthy, male, and female, older adults.
• Healthy will be defined as screen by the 2020 PAR-Q+, medical screening questionnaire, GAQ, and COVID-19 symptom questionnaire patient screening.
• 'Older' will be defined as being 65-85 years of age.
• Participants are required to not engage in structured resistance training for at least 6 months prior to participation in the study.
• Participants are willing to abide by the compliance rules of this study.

You may not qualify if:

• Pre-menopausal females: Women must be postmenopausal having not menstruated for at least 1 year prior to study participation. Hormonal fluctuations associated with the menstrual cycle have been reported to alter protein metabolism and may influence indices of muscle protein synthesis and breakdown (69-71).
• BMI \<18.5 or \> 30 kg ∙ m-2.
• Self-reported regular tobacco use and vaping products.
• Self-reported illicit drug use (e.g., growth hormone, testosterone, etc.)
• Individuals who have participated in studies within the past year involving a stable isotope of 2H.
• A history of thrombosis, diagnosed with type 2 diabetes mellitus by physician or HbA1c values of \> 7.0%, dementia, coronary artery disease, musculoskeletal/orthopedic disorders, and severe allergies.
• The use of medications known to modulate skeletal muscle metabolism (e.g., corticosteroids, hormone replacement therapy, non-steroidal anti-inflammatory drugs, metformin).
• The use of over-the-counter supplements (protein supplements, creatine, fish oil).
• Inability to adhere to any of the compliance rules judged by the principal investigator or medical doctor.

Sponsors & Collaborators

• McGill University: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Research Institute - McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

MeSH Terms

Conditions

Muscular Atrophy; Insulin Resistance; Sedentary Behavior

Interventions

Fructose; Rapeseed Oil

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Behavior

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses; Plant Oils; Oils; Lipids; Plant Preparations; Biological Products; Complex Mixtures

Study Officials

• Tyler A Churchward-Venne, PhD

  McGill University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, Investigators and Outcome Accessors will be blinded to the intervention and control drinks. The drinks will be flavor and energy matched and provided in an opaque bottle. An individual not involved with the study data collection, analysis and interpretation will be designated as a study blinder and randomizer.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized, double-blind, parallel group study design.

Study Record Dates

• First Submitted: December 12, 2022
• First Posted: January 11, 2023
• Study Start: February 27, 2023
• Primary Completion: November 15, 2023
• Study Completion: November 15, 2023
• Last Updated: February 7, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)