HealthyFATNCT04056000
Lipodystrophy and Fat Metabolism During Exercise
A study testing Caffeine, High-carbohdyrate breakfast and 60-minutes of steady state exercise in people with Healthy and Lipodystrophy, Familial Partial, run by University of Exeter at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy, Lipodystrophy, Familial Partial
- What is being tested?
- Caffeine, High-carbohdyrate breakfast and 60-minutes of steady state exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Sep 2019to 31 Dec 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Already known to researchers. Male, 29 years old.
- CONTROL SUBJECT 1
- 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
Show all 12Show fewer
- 18 - 35 years old
- Recreationally active, preferably with experience of cycling training.
- Similar (± 5 ml⋅kg-1⋅min-1) VO2max¬ to that of the participant with MDP
- 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
Who cannot join
- 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
- Any diagnosed metabolic impairment, as this may affect normal metabolism.
- Any diagnosed cardiovascular disease or hypertension to avoid any complications associated with heavy exercise.
Show all 10Show fewer
- Chronic use of any prescribed or over-the-counter pharmaceuticals.
- SUBJECT WITH FPL
- Female
- Any diagnosed cardiovascular disease or hypertension to avoid any complications associated with heavy exercise.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
School of Sport and Health Sciences
Exeter, Devon, EX4 4JA
About this study
Official title: The Regulation of Fat Metabolism in a Cyclist With Lipodystrophy: a Case Study
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.
Read more
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.
Read the 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.
- Conditions
- Healthy, Lipodystrophy, Familial Partial
- Being tested
- Caffeine, High-carbohdyrate breakfast, 60-minutes of steady state exercise
- Medical subject headings
- Lipodystrophy, Familial Partial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CaffeineDietary supplement
200 mg of caffeine, 60 minutes before exercise
High-carbohdyrate breakfastDietary supplement
Ingestion of a high-carbohydrate breakfast 60 minutes before exercise
60-minutes of steady state exerciseBehavioural
See intervention name
| Study group | Role | What they receive |
|---|---|---|
| Exercising following the ingestion of a high-carbohydrate br | Experimental | 60 minutes of cycling, with the ingestion of a high-carbohydrate breakfast and 200 mg of caffeine. Receives: Dietary Supplement: Caffeine; Dietary Supplement: High-carbohdyrate breakfast; Behavioral: 60-minutes of steady state exercise |
| Exercising following the ingestion of caffeine only | Experimental | 60 minutes of cycling, with the ingestion of 200 mg of caffeine. Receives: Dietary Supplement: Caffeine; Behavioral: 60-minutes of steady state exercise |
| Exercising in the absence of breakfast or caffeine ingestion | Experimental | 60 minutes of cycling, without the ingestion of breakfast, or caffeine. Receives: Behavioral: 60-minutes of steady state exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Throughout the 60 minute cycle
Secondary outcomes (4)
Heart rate
Heart rate will be measured throughout with the use of a heart rate monitor.
Measured: Throughout the 60 minute cycle
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.
Measured: Throughout the 60 minute cycle
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.
Measured: Throughout the 60 minute cycle
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.
Measured: Throughout the 60 minute cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2019
- Study start1 Sep 2019 (estimated)
- Primary completion31 Dec 2019 (estimated)
- Study completion31 Dec 2019 (estimated)
Why it stopped: ethical and governance issues not resolved
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Exeter
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrew Davenport, MSc, Principal investigator, The University of Exeter
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04056000
- Sponsor's protocol ID
- 258840
- Acronym
- FAT
- Status last verified
- Aug 2021
- First submitted
- 23 May 2019
- Last updated
- 31 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Regulation of Fat Metabolism in a Cyclist With Lipodystrophy: a Case Study
- ClinicalTrials.gov ID
- NCT04056000
- Acronym / sponsor ID
- FAT / 258840
- Conditions
- Healthy, Lipodystrophy, Familial Partial
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: ethical and governance issues not resolved
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of ExeterUniversity, hospital or other
- Study start
- 1 Sep 2019 (estimated)
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 14 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Exercising following the ingestion of a high-carbohydrate br | Experimental | Dietary Supplement: Caffeine, Dietary Supplement: High-carbohdyrate breakfast, Behavioral: 60-minutes of steady state exercise60 minutes of cycling, with the ingestion of a high-carbohydrate breakfast and 200 mg of caffeine. |
| Exercising following the ingestion of caffeine only | Experimental | Dietary Supplement: Caffeine, Behavioral: 60-minutes of steady state exercise60 minutes of cycling, with the ingestion of 200 mg of caffeine. |
| Exercising in the absence of breakfast or caffeine ingestion | Experimental | Behavioral: 60-minutes of steady state exercise60 minutes of cycling, without the ingestion of breakfast, or caffeine. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Already known to researchers. Male, 29 years old.
- CONTROL SUBJECT 1
- Highly trained, elite-level cyclist (VO2max > 80 ml/kg/min)
- Registered with, and racing under the jurisdiction of, British Cycling
- ~< 10% of body fat
Key exclusion criteria (10 listed)
- 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
- Any diagnosed metabolic impairment, as this may affect normal metabolism.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Caffeine200 mg of caffeine, 60 minutes before exercise | Dietary supplement | Exercising following the ingestion of a high-carbohydrate br, Exercising following the ingestion of caffeine only |
| High-carbohdyrate breakfastIngestion of a high-carbohydrate breakfast 60 minutes before exercise | Dietary supplement | Exercising following the ingestion of a high-carbohydrate br |
| 60-minutes of steady state exerciseSee intervention name | Behavioural | 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 |
Primary outcome
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
4 secondary outcomes
Heart rate
Time frame: Throughout the 60 minute cycle
Plasma glucose concentrations
Time frame: Throughout the 60 minute cycle
Plasma lactate concentrations
Time frame: Throughout the 60 minute cycle
Plasma NEFA concentrations
Time frame: Throughout the 60 minute cycle
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew Davenport, MSc principal investigator
The University of Exeter
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Caffeine, High-carbohdyrate breakfast and 60-minutes of steady state exercise in people with Healthy and Lipodystrophy, Familial Partial, run by University of Exeter at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 31 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Substrate utilisation (time frame: Throughout the 60 minute cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2021.