Glycogen Storage Disease Type III
Conditions
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTFAXE Kondi
Sucrose and glucose containing softdrink
DIETARY_SUPPLEMENTFaxe Kondi Free
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.
Sponsors
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| maximal work capacity | After up to 1 hour of bicycling on the 2nd and 4th day. | Area Under the Curve (AUC) = resistance times duration of workout |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak workload | After up to 1 hour of cycling on the 2nd and 4th day. | (Wpeak) |
| Peak respiratory exchange ratio | After up to 1 hour of cycling on the 2nd and 4th day. | (RER) |
| Peak oxygen consumption | After up to 1 hour of cycling on the 2nd and 4th day. | (VO2peak) |
| Heart rate | Continously during the cycle test (max. 1 hour) on the 2nd and 4th day | pulsemonitoring |
| Borg score | Measured periodically during the cycle test (max. 1 hour) on the 2nd and 4th day | Rate of percieved exertion |
| 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. | Analysis of blood sample |
Other
| Measure | Time frame | Description |
|---|---|---|
| p-insulin | measured at rest and max on day 1 and before exercise and every 10 minutes during exercise at day 2 and 4. | analysis of blood sample |
| p-glucagon | measured at rest and max on day 1, and before exercise, at 10 minutes, 20 min of exercise and at max on day 2 and 4. | analysis of blood sample |
| Respiratory exchange ratio, RER | measured continously during the exercise test day 2 and 4. | VO2/VCO2 |
| Hypoglycemic episodes | 2 hour observation after each of the two exercise test. | Clinical observation as well as blood glucose levels monitored during exercise tests |
| p-catecholamines | measured at rest and max on day 1, and before exercise, at 10 minutes, 20 min of exercise and at max on day 2 and 4. | analysis of blood sample |
| p-glucose | 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. | Analysis of blood sample |
| Pain | Assessed on days 3 and 5 of the trial | Pain assessed on a visual analog scale (VAS) with a scale of 0 to 10 cm |
| Fatigue | Assessed on days 3 and 5 of the trial | Fatigue Severity Score (FSS) |
| p-Creatine kinase | measured on day 1, 3 and 5. | To asses muscle damage |
| p-myoglobin | measured on day 1, 3 and 5. | To asses muscle damage |
| p-ammonia | measured at rest and max on day 1, and before exercise, at 10 minutes, 20 min of exercise and at max on day 2 and 4. | Analysis of blood sample |
Countries
Denmark
Outcome results
None listed