Exercise Effects in Huntington's Disease
- Conditions
- Huntington's Disease
- Interventions
- Behavioral: Exercise training
- Registration Number
- NCT01879267
- Lead Sponsor
- University of Zurich
- Brief Summary
Huntington's disease (HD) is an incurable and fatal disorder characterised by progressive degeneration of the basal ganglia and the cerebral cortex. Contrary to earlier thinking, HD is associated with abnormalities in peripheral tissues which might even contribute to brain pathology including muscle wasting, mitochondrial abnormalities, and impaired muscle energy metabolism. Mitochondrial impairment and muscle atrophy in human HD patients and murine models of HD are associated with altered expression of PGC-1a, a transcriptional cofactor that seems to regulate many, if not all of the adaptations of muscle fibres to chronic endurance training, and induces improved exercise performance and increased peak oxygen uptake. We aim at investigating whether endurance exercise has the capability of stabilizing and / or reversing PGC-1a dependent alterations of muscle function and structure in HD patients, and whether muscle training ameliorates musculoskeletal and cardiovascular function, as well as motor and cognitive symptoms in HD patients.
- Detailed Description
Huntington disease (HD) is an incurable and fatal disorder that affects muscle function and leads to cognitive decline and dementia. HD was long considered a brain disorder but meanwhile it was shown that HD also affects other tissues such as muscle, leading to muscle wasting. Previous studies suggested that the muscle disorder might be caused by an impaired energy metabolism through mitochondrial dysfunction, which also might also contribute to brain pathology.
In muscle tissue of healthy persons, a protein named PGC 1- α seems to regulate many, if not all of the adaptations of muscle metabolism and mitochondrial biogenesis to chronic endurance training. It was shown that PGC 1- α is reduced in muscle tissue of human HD patients and animal models of HD.
We aim investigating whether endurance exercise has the capability of stabilizing and / or reversing PGC-1α dependent decline of muscle function and structure in HD patients, and whether muscle training ameliorates muscular and cardiovascular function, as well as coordination and cognitive decline in HD. To this end, we will train 20 male HD patients using a 6 months progressive endurance exercise program. In order to compare the size effect of exercise between HD patients and healthy individuals, 20 age-matched healthy males will perform the identical exercise regimen as HD patients. Within one week before the training period starts and within one week after it has ended, we will assess metabolic and functional data. In addition, we will analyze muscle tissue samples for muscle fiber structure, metabolic phenotype and cellular pathology. Finally, gene and protein expression analyses will be performed on muscle tissue extracts to gain insights into the molecular regulation of training adaptations in HD.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Exercise Training: healthy subjects Exercise training 6 months of exercise training (2 times 30 min per week) Exercise Training: HD subjects Exercise training Endurance exercise for 6 months (30 min per week) starting one week after a 6-months natural course observation
- Primary Outcome Measures
Name Time Method Change in Unified Huntington's Disease Rating Scale (UHDRS) Baseline and 6 months
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
University Hospital Zurich, Division of Neurology
🇨🇭Zurich, ZH, Switzerland