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Metabolism, Inborn ErrorsNCT02635269

Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy

A study testing Sugar in people with Metabolism, Inborn Errors and Lipid Metabolism, Inborn Errors, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study aims to characterize the pathophysiological mechanisms of 21 different metabolic myopathies. The study will focus on exercise capacity and the metabolic derangement during exercise. Read more about this study

Who is it for?
Ages 15 to 80 yearsHealthy volunteers can take part
What is being tested?
Sugar
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteDenmark
Study dates
Jan 2016to Dec 2020
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 15 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

  • Men and women with genetically and/or biochemically verified LCHAD Deficiency
  • Healthy controls needs to be healthy to be included, evaluated by the investigator.

Who cannot join

  • Competing conditions at risk of compromising the results of the study.
  • Pregnancy or breastfeeding
  • Cardiac or pulmonary disease contraindicating peak exercise testing or strenuous exercise.
  • Inability to understand the purpose of the trial or corporate for the conduction of the experiments.
  • Veins that are too difficult to puncture for blood sampling or insertion of intravenous catheters, evaluated by the investigator
  • Moderate to severe muscle weakness, that prevents the subject completing 10 minutes of cycle-ergometry exercise at 60-70 % of VO2peak, evaluated by the investigator.
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  • Participation in other trials that may interfere with the results.
  • Intake of medications that may interfere with the results or may compromise exercise performance, as evaluated by the investigators.
  • Donation of blood within 30 days prior to conduction of the tests on test day 1.

Trial locations and contacts

1 site in 1 country.

Denmark1 site
  • Neuromuscular Research Unit, 3342

    Copenhagen, DK-2100

Other trials in Denmark

About this study

This study aims to characterize the pathophysiological mechanisms of 21 different metabolic myopathies. The study will focus on exercise capacity and the metabolic derangement during exercise.

Read the detailed description

Patients will be compared to a group of matched healthy control subjects (matched for age, gender, physical activity level and BMI) for comparison of the primary and secondary outcome measures.

Methods:

Each subject will go through 3 test days.

Test day 1:

  • International Physical Activity Questionnaire (IPAQ). The results will be used to match the patients to control subjects.
  • DEXA-scan. This is used to estimate the volume of distribution for stable isotope tracers.
  • Maximal oxidative capacity test (max-test). On a cycle ergometer, subjects will exercise for approximately 15 minutes with increasing resistance until exhaustion. The peak oxidative and workload capacities will be compared to the healthy controls and will be used to find the workload that corresponds to 55-65 % of VO2max used in the following exercise tests.
  • Blood samples. Samples will be drawn before exercise and at exhaustion and will be analyzed for the plasma concentrations of glucose, lactate, ammonia, creatine kinase and myoglobin.

Test day 2:

•Long exercise test #1. The purpose of this test is to measure the total fat and sugar oxidation rates during exercise by using stable isotope tracers.

Subjects arrive at the laboratory after 3-9 hours of fasting. One IV-catheter is inserted in the cubital vein in one arm and another in a peripheral vein in the other hand. The stable isotope tracers will be given in the cubital vein as a constant infusion of solutions of:

  • [U-13C]-palmitate (0.0026 mg x kg-1 x min-1, after a priming bolus of 0.085 mg x kg-1 NaH13CO3)
  • [1,1,2,3,3-2H5]-glycerol (0.0049 mg x kg-1 x min-1 )
  • [6.6-2H2]-glucose (0.0728 mg x kg-1 x min-1 ) For two hours the subjects rests while receiving the infusions until the tracers have distributed in the body and reached a steady state. After the rest, the subjects exercise on the cycle-ergometer until exhaustion or for a maximum of 1 hour at an intensity that corresponds to 55-65% of VO2max.

The heart rate is continuously measured during exercise, and every other minute the subject evaluates his/her degree of exertion (Rate of Perceived Exertion, RPE) on a Borg scale.

•Blood and breath samples From 20 minutes before exercise and every ten minutes until the end of exercise, blood samples are drawn and samples of the expired breath are collected.The breath is analysed for 13CO2 -enrichment. The blood is analysed for the plasma concentrations of glucose, lactate, ammonia, creatine kinase and myoglobin.

Test day 3:

•Long exercise test #2. The purpose of this test is to investigate exercise capacity and performance measured as HR, VO2 and RPE during prolonged exercise. To mimic the conditions for the working muscles in healthy persons who have an intact metabolism, the patients are given an infusion of a 10% glucose solution to maintain the blood sugar while exercising.

Subjects arrive at the laboratory after 3-9 hours fasting. After 2 hours of rest, the subjects exercise on the cycle-ergometer until exhaustion or for a maximum of 1 hour at an intensity that corresponds to 60-65% of VO2max, like they did on test day 2. This time the subjects are not given stable isotope tracers. 10 minutes before exercising, the subjects are given a bolus of glucose solution 0.2 g/kg in a cubital vein catheter and a constant infusion of 10% glucose solution is started (100ml/h). The infusion continues throughout the exercise period.

Assessments of heart rate, Rate of Perceived Exertion and blood sampling follow the same protocol as on test day 1, except no breath samples are taken and no analyses of stable isotopes are made, since the tracers are not used on test day 3.

  • Blood samples. From 20 minutes before exercise and every ten minutes until the end of exercise, blood samples are drawn. The blood is analysed for the plasma concentrations of glucose, lactate, ammonia, creatine kinase and myoglobin.
  • Muscle Biopsy At the end of test day 1 the investigators will perform a voluntary muscle biopsy.

Statistical Methods:

The investigators will use a paired t-test, two-tailed testing (or the corresponding non-parametric test, if the assumption of normality is not met). A p-value of < 0.05 will be considered significant. Results will be reported with Confidence Intervals of the difference in means. SigmaPlot version 11.0 (or a similar statistical program) will be used for statistical analysis.

No interim analyses will be made during the 4 days trial period. In the case, that a patient withdraws/is withdrawn, the obtained data from the completed tests will be included in the analyses. Raw data that is clearly and indisputably a result of an error in measurement will not be included (evaluated by the investigator). Missing or lost data will if possible be reassessed.

Being tested
Sugar
Keywords
Ergometry, Stable isotope tracers
Medical subject headings
Metabolism, Inborn Errors, Lipid Metabolism, Inborn Errors, Carbohydrate Metabolism, Inborn Errors, Trifunctional Protein Deficiency With Myopathy And Neuropathy, Carnitine palmitoyl transferase 2 deficiency, VLCAD deficiency, Medium chain acyl CoA dehydrogenase deficiency, Multiple Acyl Coenzyme A Dehydrogenase Deficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SugarOther

    Also called 10 % glucose infusion

    10 minutes before exercising, the subjects are given a bolus of glucose solution 0.2 g/kg in a cubital vein catheter and a constant infusion of 10% glucose solution is started (100ml/h). The infusion continues throughout the exercise period.

Study groups in NCT02635269
Study groupRoleWhat they receive
SugarExperimentalThe subjects exercise on the cycle-ergometer until exhaustion or for a maximum of 1 hour at an intensity that corresponds to 60-65% of VO2max.
Receives: Other: Sugar

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Total fat oxidation (rate of disappearance) during prolonged moderate intensity exercise. Measured as micro mol per kg per minute.

    Measured using stable isotope technique ([U-13C]-palmitate, [1,1,2,3,3-2H5]-glycerol and [6.6-2H2]-glucose ) and indirect calorimetry.

    Measured: Measured at at time (minutes) -120, -20, -10, 0, 10, 20, 30, 40, 50, 60. Zero is the indicatet start of 1 hour cycling test. Measured on day 2 of participation

Secondary outcomes (7)
  1. Maximal oxidative capacity (mL*kg-1*minutes-1)

    Oxidative capacity is measured continuously during a maximum exercise test on the first day of the trial. The test lasts about 15 minutes (when the participant is fully exhausted). The maximal oxidative capacity is the peak measure during the test.

    Measured: Day 1 of participation

  2. Endurance measured as minutes:seconds

    During 1 hour cycling test 1 and 1 hour cycling test 2 on day 2 and 4 of participation. The test will last for 1 hour or until exhaustion. Endurance will be defined as the total exercise duration.

    Measured: Day 2 and 4 of participation

  3. Heart rate (HR) during prolonged exercise, with and without blood sugar maintained by an infusion of a 10% glucose solution. Measured in beats per minute.

    During 1 hour cycling at 55-65% of VO2max the heart rate is measured every 2 minuts.

    Measured: During 1 hour cycling test 1 and 1 hour cycling test 2 on day 2 and 4 of participation.

  4. Oxygen consumption rate (VO2) during prolonged exercise, with and without blood sugar maintained by an infusion of a 10% glucose solution. Measured in mL.

    During 1 hour cycling at 55-65% of VO2max the oxygen consumption rate is continuously measured.

    Measured: During 1 hour cycling test 1 and 1 hour cycling test 2 on day 2 and 4 of participation.

  5. Self-evaluated exertion (Rate of Perceived Exertion (RPE)) during prolonged exercise, with and without blood sugar maintained by an infusion of a 10% glucose solution. Measured using a Borg-scale (6-20).

    During 1 hour cycling at 55-65% of VO2max the participant is asked to rate their exertion every 2 minutes.

    Measured: During 1 hour cycling test 1 and 1 hour cycling test 2 on day 2 and 4 of participation.

  6. Maximal workload capacity. Measured in watt

    The participant will be cycling at incremental workload until exhaustion. The test lasts about 15 minutes (when the participant is fully exhausted). The maximal workload is the peak measure at the end of the test.

    Measured: Day 1 of participation

  7. Total glucose oxidation (rate of disappearance) during prolonged moderate intensity exercise. Measured as micro mol per kg per minute.

    Measured using stable isotope technique ([U-13C]-palmitate, [1,1,2,3,3-2H5]-glycerol and [6.6-2H2]-glucose ) and indirect calorimetry.

    Measured: Measured at at time (minutes) -120, -20, -10, 0, 10, 20, 30, 40, 50, 60. Zero is the indicatet start of 1 hour cycling test. Measured on day 2 of participation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Dec 2015 (estimated)
  2. Study startJan 2016
  3. Primary completionAug 2020 (estimated)
  4. Study completionDec 2020 (estimated)

Resources

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
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02635269
Sponsor's protocol ID
Metabolic Myopathy
Other IDs
H-15015150
Status last verified
Oct 2019
First submitted
9 Dec 2015
Last updated
16 Oct 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Oldfors A, DiMauro S. New insights in the field of muscle glycogenoses. Curr Opin Neurol. 2013 Oct;26(5):544-53. doi: 10.1097/WCO.0b013e328364dbdc.

    PubMed 23995275
  • Liang WC, Nishino I. State of the art in muscle lipid diseases. Acta Myol. 2010 Oct;29(2):351-6.

    PubMed 21314018
  • Orngreen MC, Duno M, Ejstrup R, Christensen E, Schwartz M, Sacchetti M, Vissing J. Fuel utilization in subjects with carnitine palmitoyltransferase 2 gene mutations. Ann Neurol. 2005 Jan;57(1):60-6. doi: 10.1002/ana.20320.

    PubMed 15622536
  • Raaschou-Pedersen D, Madsen KL, Stemmerik MG, Eisum AV, Straub V, Vissing J. Fat oxidation is impaired during exercise in lipin-1 deficiency. Neurology. 2019 Oct 8;93(15):e1433-e1438. doi: 10.1212/WNL.0000000000008240. Epub 2019 Sep 6.

    PubMed 31492716
  • Madsen KL, Stemmerik MG, Buch AE, Poulsen NS, Lund AM, Vissing J. Impaired Fat Oxidation During Exercise in Long-Chain Acyl-CoA Dehydrogenase Deficiency Patients and Effect of IV-Glucose. J Clin Endocrinol Metab. 2019 Sep 1;104(9):3610-3613. doi: 10.1210/jc.2019-00453.

    PubMed 30990523

Questions about this trial

What is this clinical trial studying?

A study testing Sugar in people with Metabolism, Inborn Errors and Lipid Metabolism, Inborn Errors, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

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 2 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 16 Oct 2019. 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 Denmark. 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?

Results are not available in the source record.

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?

Total fat oxidation (rate of disappearance) during prolonged moderate intensity exercise. Measured as micro mol per kg per minute. (time frame: Measured at at time (minutes) -120, -20, -10, 0, 10, 20, 30, 40, 50, 60. Zero is the indicatet start of 1 hour cycling test. Measured on day 2 of participation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02635269, which also lists 5 linked publications.

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 16 Oct 2019.

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