Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy

NCT02635269 | Unknown

• 2 other identifiers: Metabolic MyopathyH-15015150
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metabolism, Inborn Errors; Lipid Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency; Glycogenin-1 Deficiency (Glycogen Storage Disease Type XV); Carnitine Palmitoyl Transferase 2 Deficiency; VLCAD Deficiency; Medium-chain Acyl-CoA Dehydrogenase Deficiency; Multiple Acyl-CoA Dehydrogenase Deficiency; Carnitine Transporter Deficiency; Neutral Lipid Storage Disease; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Muscle Phosphofructokinase Deficiency; Phosphoglucomutase 1 Deficiency; Phosphoglycerate Mutase Deficiency; Phosphoglycerate Kinase Deficiency; Phosphorylase Kinase Deficiency; Beta Enolase Deficiency; Lactate Dehydrogenase Deficiency; Glycogen Synthase Deficiency

Keywords

Ergometry; Stable isotope tracers

Outcome Measures

Primary Outcomes (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 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)

• Maximal oxidative capacity (mL*kg-1*minutes-1)

  Day 1 of participation

• Endurance measured as minutes:seconds

  Day 2 and 4 of participation

• 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 test 1 and 1 hour cycling test 2 on day 2 and 4 of participation.

• 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 test 1 and 1 hour cycling test 2 on day 2 and 4 of participation.

• 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 test 1 and 1 hour cycling test 2 on day 2 and 4 of participation.

Study Arms (1)

Sugar

EXPERIMENTAL

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.

Other: Sugar

Interventions

Sugar OTHER

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.

Also known as: 10 % glucose infusion

Sugar

Eligibility Criteria

• Age: 15 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Neuromuscular Research Unit, 3342

Copenhagen, DK-2100, Denmark

Location

Related Publications (5)

• 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.

  PMID: 23995275 BACKGROUND

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

  PMID: 21314018 BACKGROUND

• 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.

  PMID: 15622536 BACKGROUND

• 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.

  PMID: 31492716 DERIVED

• 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.

  PMID: 30990523 DERIVED

MeSH Terms

Conditions

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; Systemic carnitine deficiency; Chanarin-Dorfman Syndrome; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Glycogen Storage Disease Type VII; Glycogen Storage Disease XIV; Dimauro disease; Phosphoglycerate Kinase 1 Deficiency; Glycogen Storage Disease Type Ix; Glycogen Storage Disease XIII; Lactate Dehydrogenase Deficiency

Interventions

Sugars

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders; Amino Acid Metabolism, Inborn Errors; Mitochondrial Diseases; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glycogen Storage Disease; Lysosomal Storage Diseases; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Carbohydrates

Study Officials

• Karen L Madsen, MD

  Neuromuscular Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 9, 2015
• First Posted: December 18, 2015
• Study Start: January 1, 2016
• Primary Completion: August 1, 2020
• Study Completion: December 1, 2020
• Last Updated: October 16, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)