Effects of Lithium and Divalproex'on Brain-Derived Neurotrophic Factor in Huntington's Disease
Status:
Completed
Trial end date:
2005-03-01
Target enrollment:
Participant gender:
Summary
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.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Neurological Disorders and Stroke (NINDS)