Ignite Creation Date:
2025-12-25 @ 12:36 AM
Ignite Modification Date:
2025-12-25 @ 10:45 PM
Study NCT ID:
NCT01879267
Status:
COMPLETED
Last Update Posted:
2018-06-13
First Post:
2012-05-24
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Exercise Effects in Huntington's Disease
Sponsor:
University of Zurich
Organization:
Study Overview
Official Title:
Exercise Effects in Huntington's Disease
Status:
COMPLETED
Status Verified Date:
2018-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: