Lipodystrophy and Fat Metabolism During Exercise (FAT)
Primary Purpose
Healthy, Lipodystrophy, Familial Partial
Status
Withdrawn
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Caffeine
High-carbohdyrate breakfast
60-minutes of steady state exercise
Sponsored by
About this trial
This is an interventional treatment trial for Healthy
Eligibility Criteria
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.
Sites / Locations
- School of Sport and Health Sciences
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Exercising following the ingestion of a high-carbohydrate br
Exercising following the ingestion of caffeine only
Exercising in the absence of breakfast or caffeine ingestion
Arm Description
60 minutes of cycling, with the ingestion of a high-carbohydrate breakfast and 200 mg of caffeine.
60 minutes of cycling, with the ingestion of 200 mg of caffeine.
60 minutes of cycling, without the ingestion of breakfast, or caffeine.
Outcomes
Primary Outcome Measures
Substrate utilisation
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:
Plasma free fatty acids
Plasma glucose
Muscle glycogen
Fat from other sources (predominantly muscle)
This will be calculated from
Plasma free fatty acid oxidation: Production of breath 13CO2 from a continuous infusion of [U-13C]palmitate
Plasma glucose oxidation: The rate of disappearance of labelled [6, 6-2H2] glucose from a continuous infusion
Muscle glycogen = Total carbohydrate oxidation - plasma glucose oxidation
Fat from other sources = total fat oxidation - plasma free fatty acid oxidation
Secondary Outcome Measures
Heart rate
Heart rate will be measured throughout with the use of a heart rate monitor.
Plasma glucose concentrations
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04056000
Brief Title
Lipodystrophy and Fat Metabolism During Exercise
Acronym
FAT
Official Title
The Regulation of Fat Metabolism in a Cyclist With Lipodystrophy: a Case Study
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Withdrawn
Why Stopped
ethical and governance issues not resolved
Study Start Date
September 1, 2019 (Anticipated)
Primary Completion Date
December 31, 2019 (Anticipated)
Study Completion Date
December 31, 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Exeter
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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?):
Do fasting and caffeine stimulate lipolysis in lipodystrophy and, if so, where is the fat coming from?
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Lipodystrophy, Familial Partial
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Exercising following the ingestion of a high-carbohydrate br
Arm Type
Experimental
Arm Description
60 minutes of cycling, with the ingestion of a high-carbohydrate breakfast and 200 mg of caffeine.
Arm Title
Exercising following the ingestion of caffeine only
Arm Type
Experimental
Arm Description
60 minutes of cycling, with the ingestion of 200 mg of caffeine.
Arm Title
Exercising in the absence of breakfast or caffeine ingestion
Arm Type
Experimental
Arm Description
60 minutes of cycling, without the ingestion of breakfast, or caffeine.
Intervention Type
Dietary Supplement
Intervention Name(s)
Caffeine
Intervention Description
200 mg of caffeine, 60 minutes before exercise
Intervention Type
Dietary Supplement
Intervention Name(s)
High-carbohdyrate breakfast
Intervention Description
Ingestion of a high-carbohydrate breakfast 60 minutes before exercise
Intervention Type
Behavioral
Intervention Name(s)
60-minutes of steady state exercise
Intervention Description
See intervention name
Primary Outcome Measure Information:
Title
Substrate utilisation
Description
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:
Plasma free fatty acids
Plasma glucose
Muscle glycogen
Fat from other sources (predominantly muscle)
This will be calculated from
Plasma free fatty acid oxidation: Production of breath 13CO2 from a continuous infusion of [U-13C]palmitate
Plasma glucose oxidation: The rate of disappearance of labelled [6, 6-2H2] glucose from a continuous infusion
Muscle glycogen = Total carbohydrate oxidation - plasma glucose oxidation
Fat from other sources = total fat oxidation - plasma free fatty acid oxidation
Time Frame
Throughout the 60 minute cycle
Secondary Outcome Measure Information:
Title
Heart rate
Description
Heart rate will be measured throughout with the use of a heart rate monitor.
Time Frame
Throughout the 60 minute cycle
Title
Plasma glucose concentrations
Description
A cannula will be used to draw blood from subjects at several time points. Whole blood samples will be analysed immediately for plasma glucose.
Time Frame
Throughout the 60 minute cycle
Title
Plasma lactate concentrations
Description
A cannula will be used to draw blood from subjects at several time points. Whole blood samples will be analysed immediately for plasma lactate.
Time Frame
Throughout the 60 minute cycle
Title
Plasma NEFA concentrations
Description
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.
Time Frame
Throughout the 60 minute cycle
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Davenport, MSc
Organizational Affiliation
The University of Exeter
Official's Role
Principal Investigator
Facility Information:
Facility Name
School of Sport and Health Sciences
City
Exeter
State/Province
Devon
ZIP/Postal Code
EX4 4JA
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
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Lipodystrophy and Fat Metabolism During Exercise
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