Effect of Lithium and Divalproex in Alzheimer's Disease
|First Submitted Date ICMJE||July 23, 2004|
|First Posted Date ICMJE||July 26, 2004|
|Last Update Posted Date||March 4, 2008|
|Start Date ICMJE||July 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 NCT00088387 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||Effect of Lithium and Divalproex in Alzheimer's Disease|
|Official Title ICMJE||Glycogen Synthetase Kinase 3 (GSK-3) Inhibition in Alzheimer's Disease|
This study will examine the effect of the drugs lithium and divalproex (Depakote) on tau proteins, a type of protein in the brain and spinal fluid that are altered in patients with Alzheimer's disease. Both drugs are approved by the Food and Drug Administration to treat mood disorders, and both have been shown in animal studies to decrease the amount of altered tau protein. This study will determine whether lithium alone or in combination with divalproex reduces the altered tau protein in the spinal fluid of patients with Alzheimer's disease.
Patients with Alzheimer's disease who are between 40 and 90 years of age may be eligible for this study. Candidates are screened with a medical history and physical examination, neurologic and neuropsychological evaluation, blood and urine tests, electrocardiogram (EKG), and, if needed, a magnetic resonance imaging (MRI) scan of the brain.
Participants undergo the following tests and procedures:
|Detailed Description||The overall objective of this study is to examine the acute effects of lithium alone and/or in combination with divalproex on surrogate measures of neuroprotective activity in patients with Alzheimer's disease. It is hypothesized that at safe and tolerable doses these drugs will inhibit glycogen synthase kinase-3 activity and reduce the phosphorylated tau epitopes threonine-181 and threonine-231 implicated in the pathogenesis of this disorder. In this proof-of-principle study, efficacy on reducing tau phosphorylated epitopes will be assessed through cerebrospinal fluid (CSF) measurements. Safety will be monitored by means of frequent clinical evaluations and laboratory tests.|
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Primary Purpose: Treatment|
|Condition ICMJE||Alzheimer Disease|
|Study Arms||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|
|Estimated Completion Date||March 2005|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Patient is between the ages of 40 and 90 (inclusive).
Patient will have a diagnosis of AD; the study will be confined to patients who are able to provide consent (pass a capacity assessment).
The modified Hachinski Ischemia Score must be less than 4.
Brain MRI performed within 15 months of enrollment must be compatible with the diagnosis of AD.
Patient and/or caregiver are willing to adhere to protocol requirements as evidenced by written, informed consent.
Patients meeting any of the following exclusion criteria during screening or during the study will not be enrolled or will be immediately excluded from the study, as appropriate:
Patient has a history of any medical condition 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. The following medications are forbidden for at least one month prior to the treatment phase (unless otherwise noted) and during the course of the study:
Any investigational drugs;
Anti-depressants (eligibility will be considered as long as dosage remains stable throughout the study);
Anticonvulsants and other mood stabilizing drugs;
Treatment that may provoke lithium toxicity due to reduced renal clearance, including metronidazole, spectinomycin, tetracycline;
Treatment that may substantially increase steady-state plasma lithium levels resulting in lithium toxicity, including angiotensin-converting enzyme inhibitors, NSAIDS, diuretics;
Treatment that may increase the risk of neurotoxicity, including calcium channel blocking agents;
Drugs that may increase urinary lithium excretion resulting in lower serum lithium concentrations, such as acetazolamide, urea, xanthine preparations, alkalinizing agents such as sodium bicarbonate, theophylline;
Drugs that interact with lithium, including methyldopa;
Neuroleptics (eligibility will be considered as long as dosage remains stable throughout the study). If patient is on existing atypical neuroleptic drugs, these will be continued at the same dose. Patients will not start a new prescription for atypical antipsychotics during the study;
Drugs that may prolong the effects of lithium, including neuromuscular blocking agents;
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.
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.
Patient's inability to swallow tablets or to comply with medication schedule.
Patient has no adequate caregiver.
Patient and/or caregiver are unwilling to sign an informed consent or to comply with protocol requirements.
Patient is unwilling to have lumbar puncture.
|Ages||Child, Adult, Senior|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00088387|
|Other Study ID Numbers ICMJE||040243
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||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|
|PRS Account||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