Exercise Effects in Huntington's Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by University of Zurich
Sponsor:
Information provided by (Responsible Party):
University of Zurich
ClinicalTrials.gov Identifier:
NCT01879267
First received: May 24, 2012
Last updated: June 12, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention
Huntington's Disease
Behavioral: Exercise training

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Exercise Effects in Huntington's Disease

Resource links provided by NLM:


Further study details as provided by University of Zurich:

Primary Outcome Measures:
  • Change in Unified Huntington's Disease Rating Scale (UHDRS) [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: January 2012
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Exercise Training: HD subjects
Endurance exercise for 6 months (30 min per week) starting one week after a 6-months natural course observation
Behavioral: Exercise training
6 months of exercise training (2 times 30 min per week) starting one week after a 6-months natural course observation period
Exercise Training: healthy subjects
6 months of exercise training (2 times 30 min per week)
Behavioral: Exercise training
6 months of exercise training (2 times 30 min per week) starting one week after a 6-months natural course observation period

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.

  Eligibility

Ages Eligible for Study:   30 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria: Inclusion criteria for HD subjects are:

  • Male gender
  • Genetically verified diagnosis of HD
  • Age 30 to 50 years
  • Presence of only mild to moderate neurological, cognitive or muscular impairment allowing the subjects to give their written informed consent and to participate in the endurance training (UHDRS 30 or lower)

For healthy control participants, inclusion criteria are:

  • male gender 9
  • age 30 to 50 years
  • absence of physical or mental illness

Exclusion criteria: Exclusion criteria for HD subjects are:

  • Female gender
  • Advanced neurological, cognitive or muscular impairment related to HD that does not allow patients to participate in the endurance training and/or to give their written informed consent
  • Cardiovascular disease or any other medical condition that might not be compatible with endurance training
  • CK levels > 300 U/L

Exclusion criteria for healthy control participants are:

  • cardiovascular disease
  • any other medical condition that might not be compatible with endurance training
  • CK levels > 300 U/L.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01879267

Contacts
Contact: Jens A Petersen, MD jens.petersen@usz.ch
Contact: Hans H Jung, MD hans.jung@usz.ch

Locations
Switzerland
University Hospital Zurich, Division of Neurology Recruiting
Zurich, ZH, Switzerland, 8091
Sponsors and Collaborators
University of Zurich
Investigators
Principal Investigator: Hans H Jung, Professor MD University Hospital Zurich, Division of Neurology
  More Information

No publications provided

Responsible Party: University of Zurich
ClinicalTrials.gov Identifier: NCT01879267     History of Changes
Other Study ID Numbers: KEK-ZH-Nr. 2009-0119
Study First Received: May 24, 2012
Last Updated: June 12, 2013
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Mental Disorders
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Chorea
Dementia
Dyskinesias

ClinicalTrials.gov processed this record on October 21, 2014