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Lipodystrophy and Fat Metabolism During Exercise (FAT)

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ClinicalTrials.gov Identifier: NCT04056000
Recruitment Status : Withdrawn (ethical and governance issues not resolved)
First Posted : August 14, 2019
Last Update Posted : August 31, 2021
Sponsor:
Information provided by (Responsible Party):
University of Exeter

Tracking Information
First Submitted Date  ICMJE May 23, 2019
First Posted Date  ICMJE August 14, 2019
Last Update Posted Date August 31, 2021
Estimated Study Start Date  ICMJE September 1, 2019
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 13, 2019)
Substrate utilisation [ Time Frame: Throughout the 60 minute cycle ]
n..b. Please be aware that the below is a single, composite measure, wherein no single outcome measure cannot exist without the other. As such, it is presented as is, below. How carbohydrate and caffeine ingestion can affect the contribution to energy expenditure during 1 hour of exercise at 55%Wmax from:
  1. Plasma free fatty acids
  2. Plasma glucose
  3. Muscle glycogen
  4. Fat from other sources (predominantly muscle)
This will be calculated from
  1. Plasma free fatty acid oxidation: Production of breath 13CO2 from a continuous infusion of [U-13C]palmitate
  2. Plasma glucose oxidation: The rate of disappearance of labelled [6, 6-2H2] glucose from a continuous infusion
  3. Muscle glycogen = Total carbohydrate oxidation - plasma glucose oxidation
  4. Fat from other sources = total fat oxidation - plasma free fatty acid oxidation
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2019)
  • Heart rate [ Time Frame: Throughout the 60 minute cycle ]
    Heart rate will be measured throughout with the use of a heart rate monitor.
  • Plasma glucose concentrations [ Time Frame: Throughout the 60 minute cycle ]
    A cannula will be used to draw blood from subjects at several time points. Whole blood samples will be analysed immediately for plasma glucose.
  • Plasma lactate concentrations [ Time Frame: Throughout the 60 minute cycle ]
    A cannula will be used to draw blood from subjects at several time points. Whole blood samples will be analysed immediately for plasma lactate.
  • Plasma NEFA concentrations [ Time Frame: Throughout the 60 minute cycle ]
    A cannula will be used to draw blood from subjects at several time points. At the end of the trial, plasma samples will be moved to a -80°C freezer for later analysis for NEFA.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lipodystrophy and Fat Metabolism During Exercise
Official Title  ICMJE The Regulation of Fat Metabolism in a Cyclist With Lipodystrophy: a Case Study
Brief Summary

Mandibular dysplasia with deafness and progeroid features (MDP) syndrome is a rare genetic metabolic disorder that causes lipodystrophy: the inability of the body to store subcutaneous adipose tissue (fat under the skin). This creates a unique scenario where any ingested fat is diverted to the abdomen and liver, often leading to diabetes.

The investigators have an opportunity to study an individual with MDP who has competed in and won national para-cycling championships and is able to prevent/control his diabetes by regular bicycle training. He has approached us for advice on nutritional strategies to improve his cycling performance, and insight into how he uses fat during exercise.

The investigators also wish to study a moderately-trained cyclist with Familial partial lipodystrophy (FPL). Those with FPL show a different pattern of lipodystrophy than those with MDP, allowing us to further increase the investigator's understanding of fat utilisation in those with lipodystrophy during exercise.

The investigators know how subcutaneous fat is used during exercise, and how duration, nutrition, carbohydrate availability, and exercise intensity can affect this. The investigators aim to investigate these processes during exercise in MDP and FPL. This will potentially provide nutrition and performance advice to the individuals, and insight on fat use in lipodystrophy and diabetes.

Detailed Description

During prolonged sub-maximal endurance exercise, both fat and carbohydrate are readily used substrates. The relative contribution and regulation of either is dependent on substrate availability (endogenous and exogenous), the duration of exercise, and the intensity of exercise. For example, exercising under fasted or caffeine supplemented conditions increases adipose tissue lipolysis, free fatty acid availability, and thus fat utilisation, whilst exercising under fed or carbohydrate loaded conditions increases glucose availability from elevated liver and muscle glycogen stores, and thus carbohydrate utilisation. This is important during prolonged sub-maximal exercise because when the limited endogenous carbohydrate stores are depleted, the body must rely more on fat. However, it is not known whether this regulation is present in conditions such as MDP and FPL where there is essentially no adipose tissue.

The investigators have an opportunity to study an individual with MDP who has competed in and won national para-cycling championships. He has approached us for advice on nutritional strategies to improve his cycling performance, and insight into how he uses fat during exercise. Intriguingly, the individual has provided anecdotal evidence that exercising under fasted conditions severely impairs his performance but that the use of caffeine improves his performance. He also states that he uses carbohydrate feeding strategies before and during prolonged exercise but is unsure whether it helps or not. This raises two fundamental questions that should be answered before any nutritional advice should be given (e.g. should a pre-exercise fat feeding or low glycemic index carbohydrate strategy be adopted?):

  1. Do fasting and caffeine stimulate lipolysis in lipodystrophy and, if so, where is the fat coming from?
  2. Does carbohydrate feeding before exercise impair lipolysis in lipodystrophy?

In order to answer these questions, the investigators need to directly measure rates of fat and carbohydrate utilisation from the circulation and muscle stores during exercise in the individual and a control participant using a stable isotope infusion approach. As well as providing results of significant scientific interest to the lipodystrophy field (researchers, clinicians, patients) and answering fundamental exercise physiology questions on substrate availability, the investigators hope that the outcomes will offer a substantial platform for improving the participant's knowledge of exercise nutrition and exercise performance.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Healthy
  • Lipodystrophy, Familial Partial
Intervention  ICMJE
  • Dietary Supplement: Caffeine
    200 mg of caffeine, 60 minutes before exercise
  • Dietary Supplement: High-carbohdyrate breakfast
    Ingestion of a high-carbohydrate breakfast 60 minutes before exercise
  • Behavioral: 60-minutes of steady state exercise
    See intervention name
Study Arms  ICMJE
  • Experimental: Exercising following the ingestion of a high-carbohydrate br
    60 minutes of cycling, with the ingestion of a high-carbohydrate breakfast and 200 mg of caffeine.
    Interventions:
    • Dietary Supplement: Caffeine
    • Dietary Supplement: High-carbohdyrate breakfast
    • Behavioral: 60-minutes of steady state exercise
  • Experimental: Exercising following the ingestion of caffeine only
    60 minutes of cycling, with the ingestion of 200 mg of caffeine.
    Interventions:
    • Dietary Supplement: Caffeine
    • Behavioral: 60-minutes of steady state exercise
  • Experimental: Exercising in the absence of breakfast or caffeine ingestion
    60 minutes of cycling, without the ingestion of breakfast, or caffeine.
    Intervention: Behavioral: 60-minutes of steady state exercise
Publications * Not Provided

*   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 Withdrawn
Actual Enrollment  ICMJE
 (submitted: August 25, 2021)
0
Original Estimated Enrollment  ICMJE
 (submitted: August 13, 2019)
5
Estimated Study Completion Date  ICMJE December 31, 2019
Estimated Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

SUBJECT WITH FPL

Inclusion:

• Already known to researchers. Male, 29 years old.

CONTROL SUBJECT 1

Inclusion:

  • Highly trained, elite-level cyclist (VO2max > 80 ml/kg/min)
  • Registered with, and racing under the jurisdiction of, British Cycling
  • ~< 10% of body fat
  • Male
  • 18 - 35 years old

Exclusion:

  • Any diagnosed metabolic impairment, as this may affect normal metabolism.
  • Any diagnosed cardiovascular disease or hypertension to avoid any complications associated with heavy exercise.
  • Chronic use of any prescribed or over-the-counter pharmaceuticals.

CONTROL SUBJECT 2

Inclusion:

  • Recreationally active, preferably with experience of cycling training.
  • Similar (± 5 ml⋅kg-1⋅min-1) VO2max¬ to that of the participant with MDP

Exclusion:

  • Any diagnosed metabolic impairment, as this may affect normal metabolism.
  • Any diagnosed cardiovascular disease or hypertension to avoid any complications associated with heavy exercise.
  • Chronic use of any prescribed or over-the-counter pharmaceuticals.

SUBJECT WITH FPL

Inclusion:

  • Recreationally active, preferably with experience of cycling training.
  • Similar (± 5 ml⋅kg-1⋅min-1) VO2max¬ to that of the participant with MDP
  • Diagnosis with FPL

Exclusion:

  • Female
  • Any diagnosed cardiovascular disease or hypertension to avoid any complications associated with heavy exercise.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 35 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04056000
Other Study ID Numbers  ICMJE 258840
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Exeter
Study Sponsor  ICMJE University of Exeter
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andrew Davenport, MSc The University of Exeter
PRS Account University of Exeter
Verification Date August 2021

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