Determining the Muscle Anabolic Properties of Phosphatidic Acid.

NCT03446924 | Completed

• 1 other identifier: RG_14-192
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Ageing is characterized by a loss of muscle mass that is detrimental for physical function and metabolic health and increases the risk of mortality. The loss of muscle protein mass with ageing is characterized by a blunted muscle anabolic response to nutrition and exercise. Thus, interventions to counteract muscle anabolic blunting in old age might assist in the long-term maintenance of muscle mass. Phosphatidic acid (hereafter defined as 'PA') is a novel nutrient compound that has been suggested to play an important role in muscle growth. Oral consumption of PA may amplify the signalling response to nutrition and exercise and restore muscle anabolic sensitivity in older adults. In order for PA to be 'clinically' applied as a means to mitigate muscle loss in aged populations, we must first understand the efficacy and mechanisms underlying the anabolic properties of this compound, which have yet to be defined in man. The proposed pilot study is needed to investigate the acute muscle metabolic properties of oral PA supplementation in older individuals. Sixteen healthy (non-obese, non-diabetic, non-smokers) older males aged 65-75 yrs will initially complete a lower-limb strength assessment and undergo a body composition scan. Between 4-14 days after these initial assessments, participants will be assigned to co-ingest 1.5g of either phosphatidic acid (N= 8; PA) or a non-caloric placebo (N=8; PL) after following a bout of moderate intensity, single leg resistance exercise. A stable isotope infusion will be combined with serial muscle biopsies from the thigh of each leg to determine the measure rates of muscle protein synthesis in the fasted state and in the 'early' and 'late' phase of feeding-only and exercise-plus-feeding.

Conditions

Sarcopenia

Keywords

Nutraceuticals; Muscle anabolism; Ageing

Outcome Measures

Primary Outcomes (1)

• Myofibrillar protein synthesis in response to oral phosphatidic acid or placebo ingestion alone or in combination with resistance exercise

  Myofibrillar protein synthesis will be determined via mass spectrometry to assess stable isotope enrichment of 13C6 phenylalanine isotope in the myofibrillar protein fraction of biopsy tissue. The standard precursor-product calculations will be applied, using plasma isotope enrichment as the precursor.

  The change in myofibrillar protein synthesis after treatment ingestion will be determined over 0-to-2.5 hours and 2.5-to-5 hours post-ingestion in rested and exercised legs

Secondary Outcomes (1)

• Anabolic and proteolytic signalling phosphorylation

  The change in signaling protein phosphorylation from rest will be measured at 2.5 and 5 h after treatment ingestion in rested and exercised legs

Study Arms (2)

Control

PLACEBO COMPARATOR

The control group will be given a single dose of 1.5 g rice flour in capsule form (250 mg / capsule). The gelatine capsules (MyProtein, Northwich, UK) used are identical to those used in the treatment group. Capsules are prepared by the investigatory team using good hygiene practice in the research kitchen of the School of Sport, Exercise and Rehabilitation (University of Birmingham).

Dietary Supplement: Rice flour

Treatment

ACTIVE COMPARATOR

The treatment group will be given a single dose of 1.5g phosphatidic acid in capsule form (250 mg / capsule). Capsules are prepared by the investigatory team using good hygiene practice in the research kitchen of the School of Sport, Exercise and Rehabilitation (University of Birmingham). PA is considered a dietary supplement ingredient according to the US FDA. The source of PA will be a commercial available soy-derived PA (Mediator®, Chemi Nutra, White Bear Lake, MN). The safety of Mediator® Soy-PA has been thoroughly demonstrated in humans. Mediator® Soy-PA does not contain any compounds with narcotic, psychotropic or pharmaceutical effects and is in compliance with banned substances requirements as espoused by the World Anti-Doping Agency. Mediator® Soy-PA is not a medicinal product.

Dietary Supplement: Phosphatidic Acid

Interventions

Phosphatidic Acid DIETARY_SUPPLEMENT

To be administered a single dose of 1.5 g phosphatidic acid in capsule form (250 mg / capsule).

Treatment

Rice flour DIETARY_SUPPLEMENT

Rice flour placebo to be administered a single dose of 1.5 g in capsule form (250 mg / capsule).

Control

Eligibility Criteria

• Age: 65 Years - 80 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Be a non-smoking male between 65 and 80 years.
• Have a BMI between 18 and 25 kg/m2.
• Be in good general health: no cardiovascular or metabolic diseases.

You may not qualify if:

• Health problems such as: heart disease, rheumatoid arthritis, uncontrolled hypertension, poor lung function, or any health condition that might put you at risk when participating in this study.
• Generalised neuromuscular disease (such as Parkinson's disease or motorneurone disease).
• Failure to obtain clearance for exercise participation from your GP or negative advice given by your GP concerning exercise participation.
• Involvement in regular structured resistance exercise training at the time of the study.
• Consumption of any analgesic drugs, anti-inflammatory drugs, or medication that is known to affect protein metabolism (beta-blockers, corticosteroids, NSAIDs).
• Participants who have undergone muscle biopsy testing or isotope infusion procedures within the last 5 years.

Sponsors & Collaborators

• University of Birmingham: lead
• University of Nottingham: collaborator

Study Sites (1)

University of Birmingham, School of Sport, Exercise and Rehabilitation Sciences

Edgbaston, West Midlands, B15 2TT, United Kingdom

Location

Related Publications (1)

• Smeuninx B, Nishimura Y, McKendry J, Limb M, Smith K, Atherton PJ, Breen L. The effect of acute oral phosphatidic acid ingestion on myofibrillar protein synthesis and intracellular signaling in older males. Clin Nutr. 2019 Jun;38(3):1423-1432. doi: 10.1016/j.clnu.2018.06.963. Epub 2018 Jun 21.

  PMID: 29970319 DERIVED

MeSH Terms

Conditions

Sarcopenia

Interventions

Phosphatidic Acids; Flour

Condition Hierarchy (Ancestors)

Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycerophosphates; Phospholipids; Membrane Lipids; Lipids; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: An individual with no direct study involvement will administer treatments in a double-blind manner. Investigators will be un-blinded to treatment arms upon completion of data analysis.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel-designed study in which participants will be randomized to receive phosphatidic acid or placebo treatment. A parallel design was chosen due to the number of invasive muscle biopsies performed during each experimental trial.

Study Record Dates

• First Submitted: February 15, 2018
• First Posted: February 27, 2018
• Study Start: August 1, 2015
• Primary Completion: March 1, 2017
• Study Completion: September 1, 2017
• Last Updated: February 27, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)