Effects of Lithium and Divalproex`on Brain-Derived Neurotrophic Factor in Huntington's Disease
|First Received Date ICMJE||November 2, 2004|
|Last Updated Date||March 3, 2008|
|Start Date ICMJE||October 2004|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00095355 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Effects of Lithium and Divalproex`on Brain-Derived Neurotrophic Factor in Huntington's Disease|
|Official Title ICMJE||Stimulation of Tyrosine Kinase and ERK Signaling Pathways in Huntington's Disease|
This study will examine whether lithium carbonate, given alone or with divalproex, increases the amount of brain-derived neurotrophic factor (BDNF) in the spinal fluid of patients with Huntington's disease (HD), a hereditary disorder of the central nervous system. Patients with this fatal degenerative disease have lower amounts of substances in the brain and spinal fluid called trophic or growth factors. One of these factors is BDNF. A possible treatment for HD may be to increase the levels of BDNF. Lithium carbonate, a drug used to treat bipolar disorder, and divalproex, a drug used to treat mood disorders and seizure disorders, have both been shown to increase the amount of BDNF protein in laboratory studies.
Patients 18 to 70 years old with a DNA-confirmed diagnosis of Huntington's disease may be eligible for this study. Candidates are screened with a medical history and physical examination, neurological evaluation, blood and urine tests, and electrocardiogram (EKG).
Participants take lithium carbonate with and without divalproex. They also receive placebo (an inactive substance) for portions of the study. On the first day of the study, patients are given a supply of pills with instructions on how to take them. Blood pressure and pulse are measured, and blood and urine tests may be done. Patients are evaluated with standardized tests and scales for assessment of various aspects of HD.
Patients return to the clinic once a week for follow-up evaluations, including blood and urine tests, physical examinations, disease assessments, and a review of medication side effects. Each week, they receive a new supply of medications and instructions on how to take them. At the end of the sixth week, they finish taking the medications.
During the study, patients undergo three lumbar punctures (spinal taps) - at weeks 2, 4, and 6 - to measure BDNF and various other brain chemicals. For this test, a local anesthetic is given and a needle is inserted in the space between the bones in the lower back where the CSF circulates below the spinal cord. A small amount of fluid is collected through the needle. The procedure generally takes from 5 to 20 minutes.
Patients return to the clinic 2 weeks after completing the study medication for a final evaluation, including a physical examination and blood and urine tests.
Objective: The overall objective of this study is to examine the acute effects of lithium alone and/ or in combination with divalproex on markers of neuroprotective activity in patients with Huntington's disease (HD). It is hypothesized that at safe and tolerable doses these drugs will enhance depleted levels of brain-derived neurotrophic factor (BDNF), a neurotrophin which is necessary for the survival of striatal neurons.
Study population: Patients suffering from Huntington's disease will be study participants.
Design: The acute effects of lithium and divalproex on surrogate measures of neuroprotective activity will be evaluated in up to 24 HD patients. The study, lasting approximately 6 weeks, will be conducted on an outpatient basis.
Outcome measures: In this proof-of-principle study, efficacy in restoring BDNF concentrations will be assessed through cerebrospinal fluid (CSF) measurements. Safety will be monitored by means of frequent clinical evaluations and laboratory test.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
|Condition ICMJE||Huntington's Disease|
|Study Arm (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||March 2005|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Patients meeting any of the following exclusion criteria during screening or during the study will not be immediately excluded from the study, as appropriate:
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00095355|
|Other Study ID Numbers ICMJE||050020, 05-N-0020|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Neurological Disorders and Stroke (NINDS)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||March 2005|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP