Energy Supplements to Improve Exercise Tolerance in Metabolic Myopathies

Study Overview
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Brief Summary
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Patients suffering from the metabolic myopathy Glycogen Storage Disease type IIIa (GSDIIIa) have a problem releasing sugar stored in cells that is needed for energy production. This causes several systemic impairments, but only recently have the exercise-related symptoms in the muscles been examined. A previous study showed signs that intravenous infusion of glucose relieves some of these symptoms. The purpose of this study is to investigate in a randomized and placebo-controlled fashion whether oral ingestion of sugar can alleviate muscular symptoms in patients with GSDIIIa.

Detailed Description
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It has recently been documented how patients with GSDIIIa have a moderate to severely reduced exercise capacity, and that exercise induces muscle pain and cramps. These symptoms are caused by the inability to mobilize skeletal muscle glycogen and are most likely the consequence of a severe energy deficiency within muscles. The study changed the phenotype of GSDIIIa, to include exercise-induced symptoms, which is a typical presentation in other metabolic myopathies. It also documented that exercise capacity was significantly improved while exercise-induced muscular symptoms were relieved by an intravenous glucose infusion. Based on these findings, this study wishes to investigate if oral ingestion of sucrose has the same effects on work capacity on a larger number of patients, in a randomized, placebo-controlled, cross-over setup. Ingestion of sucrose has the potential to be an effective, cheap and easily accessible dietary treatment of muscular symptoms in GSDIIIa.

Official Title
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Energy Supplements to Improve Exercise Tolerance in Metabolic Myopathies

Conditions
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Glycogen Storage Disease Type III

Intervention / Treatment
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* Dietary Supplement: FAXE Kondi
* Dietary Supplement: Faxe Kondi Free


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Genetically and/or biochemically verified GSDIIIa. 18 years or older. Exclusion Criteria: Clinically significant cardiac or pulmonary disease. Pregnancy or lactation. Severe mental disorders or participants that are in other ways unable to understand the purpose of the trials. Subjects where the investigator assess that it is not possible or very difficult to place an intravenous catheters. Other conditions of the joints or skeletal muscle such as arthritis or sprains. If the condition is expected to resolve before the study inclusion period is stopped, the subject may be included at a later time. Moderate to severe muscle weakness, where the participants are not expected to complete 10 minutes of cycle-ergometry exercise at 70 % of VO2peak. Verified diabetes. Participation in other clinical trials that may interfere with the results. Medications that may interfere with the results or increase the risk of bleeding. Blood-clotting or bleeding disorders. Blood donation one month or less prior to inclusion.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FAXE Kondi - a sugary soft-drink<br>100 ml FAXE Kondi (10 grams of carbohydrates per 100 ml) is ingested every ten minutes during exercise plus 400 ml before exercise start. | Dietary Supplement: FAXE Kondi<br>* Sucrose and glucose containing softdrink<br>|
| Placebo Comparator: FAXE Kondi Free - a sugarfree soft-drink<br>100 ml FAXE Kondi Free (0 grams of carbohydrates per 100 ml) is ingested every ten minutes during exercise plus 400 ml before exercise start. | Dietary Supplement: Faxe Kondi Free<br>* Diet softdrink with artificial sweeteners aspartame and acesulfame potassium. Both sweeteners are approved for use as food additives in the European Union and by the FDA. Aspartame metabolism is well understood and normal doses does not affect plasma concentrations of lipids, amino acids, glucose levels, key regulatory hormones or skeletal muscle metabolism. Acesulfame Potassium is not metabolized in humans and is excreted as the parent compound in urine. Since the two artificial sweeteners does not affect skeletal muscle metabolism or blood glucose levels, and both compounds have a well documented safety profiles, FAXE Kondi Free is considered to be an ideal placebo soft drink in this study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximal work capacity | Area Under the Curve (AUC) | After up to 1 hour of bicycling on the 2nd and 4th day. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak oxygen consumption | (VO2peak) | After up to 1 hour of cycling on the 2nd and 4th day. | 
| Peak workload | (Wpeak) | After up to 1 hour of cycling on the 2nd and 4th day. | 
| Peak respiratory exchange ratio | (RER) | After up to 1 hour of cycling on the 2nd and 4th day. | 
| p-lactate |  | measured at rest and max on day 1, and before first dose of soft drink, before exercise and every 10 minutes during exercise at day 2 and 4. | 
| Heart rate |  | Continously during the cycle test (max. 1 hour) on the 2nd and 4th day | 
| Borg score |  | Measured periodically during the cycle test (max. 1 hour) on the 2nd and 4th day |