Huntington's DiseasePhase 2NCT00095355
Effects of Lithium and Divalproex'on Brain-Derived Neurotrophic Factor in Huntington's Disease
A Phase 2 study testing Lithium and Divalproex in people with Huntington's Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Huntington's Disease
- What is being tested?
- Lithium and Divalproex
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2004to Mar 2005
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Subject is between the ages of 18 and 70 (inclusive);
- Subject will have a diagnosis of HD confirmed by DNA testing [prior to enrollment into the study].
- Only those subjects will be eligible, who with or without a caregiver, can be assumed to be able to comply with study requirements and to report on their condition by telephone.
- Subjects with minimental status examination score of greater than and equal to 24.
Who cannot join
- Patients meeting any of the following exclusion criteria during screening or during the study will not be immediately excluded from the study, as appropriate:
- Patient has a history of any medical condition such as diabetes, cardiac disease, renal impairment, liver disease, pancreatitis and other chronic medical problems that can reasonably be expected to subject the patient to unwarranted risk;
- Patient has clinically significant laboratory abnormalities that would preclude administration of lithium and divalproex;
- Patient is taking a prohibited concomitant medication;
- Patient has not been using an adequate contraceptive method for the last 30 days or unwilling to continue contraception throughout the study, or is not at least one year post menopausal (if female);
- Patient is pregnant or breastfeeding;
Show all 13Show fewer
- Patient has participated in a clinical study with an investigational drug within the last 30 days;
- Patient has a condition (such as active drug or alcohol abuse) that, in the opinion of the investigators, would interfere with compliance or safety;
- Patient has known hypersensitivity to lithium or divalproex;
- Patients inability to swallow tablets or to comply with medication schedule;
- Patient and / or caregiver are unwilling to sign an informed consent or to comply with protocol requirements;
- Patient is unwilling to have lumbar puncture.
- Patient with history of severe depression, or past suicide attemps.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Neurological Disorders and Stroke (NINDS)
Bethesda, Maryland, 20892
About this study
Official title: 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).
Read more
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.
Read the detailed description
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.
- Conditions
- Huntington's Disease
- Being tested
- Lithium, Divalproex
- Keywords
- BDNF, Lithium, Divalproex, Huntington Disease, HD
- Medical subject headings
- Huntington Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LithiumDrug
DivalproexDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2004 (estimated)
- Study startOct 2004
- Study completionMar 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Huntington's DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 35 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00095355
- Sponsor's protocol ID
- 050020
- Other IDs
- 05-N-0020
- Status last verified
- Mar 2005
- First submitted
- 2 Nov 2004
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Hedreen JC, Folstein SE. Early loss of neostriatal striosome neurons in Huntington's disease. J Neuropathol Exp Neurol. 1995 Jan;54(1):105-20. doi: 10.1097/00005072-199501000-00013.
PubMed 7815073A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell. 1993 Mar 26;72(6):971-83. doi: 10.1016/0092-8674(93)90585-e.
PubMed 8458085Bibel M, Barde YA. Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev. 2000 Dec 1;14(23):2919-37. doi: 10.1101/gad.841400. No abstract available.
PubMed 11114882
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stimulation of Tyrosine Kinase and ERK Signaling Pathways in Huntington's Disease
- ClinicalTrials.gov ID
- NCT00095355
- Acronym / sponsor ID
- 050020
- Conditions
- Huntington's Disease
- Keywords
- BDNF, Lithium, Divalproex, Huntington Disease, HD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Oct 2004
- Study completion
- Mar 2005
- First posted
- 3 Nov 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Subject is between the ages of 18 and 70 (inclusive);
- Subject will have a diagnosis of HD confirmed by DNA testing [prior to enrollment into the study].
- Only those subjects will be eligible, who with or without a caregiver, can be assumed to be able to comply with study requirements and to report on their condition by telephone.
- Subjects with minimental status examination score of greater than and equal to 24.
Key exclusion criteria (13 listed)
- Patients meeting any of the following exclusion criteria during screening or during the study will not be immediately excluded from the study, as appropriate:
- Patient has a history of any medical condition such as diabetes, cardiac disease, renal impairment, liver disease, pancreatitis and other chronic medical problems that can reasonably be expected to subject the patient to unwarranted risk;
- Patient has clinically significant laboratory abnormalities that would preclude administration of lithium and divalproex;
- Patient is taking a prohibited concomitant medication;
- Patient has not been using an adequate contraceptive method for the last 30 days or unwilling to continue contraception throughout the study, or is not at least one year post menopausal (if female);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lithium | Drug | – |
| Divalproex | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 7815073Hedreen JC, Folstein SE. Early loss of neostriatal striosome neurons in Huntington's disease. J Neuropathol Exp Neurol. 1995 Jan;54(1):105-20. doi: 10.1097/00005072-199501000-00013.
- Background: PubMed 8458085A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell. 1993 Mar 26;72(6):971-83. doi: 10.1016/0092-8674(93)90585-e.
- Background: PubMed 11114882Bibel M, Barde YA. Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev. 2000 Dec 1;14(23):2919-37. doi: 10.1101/gad.841400. No abstract available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lithium and Divalproex in people with Huntington's Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00095355, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008; AzTrials last refreshed its copy on 7 Nov 2026.