Effect of Lithium and Divalproex in Alzheimer's Disease

Alzheimer Disease Clinical Trial

Official title: Glycogen Synthetase Kinase 3 (GSK-3) Inhibition in Alzheimer's Disease

Status Completed

Clinical Trial Summary

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:

• Drug treatment: Patients take study drugs for 6 weeks.

• Weekly clinic visits: Patients come to the clinic once a week for a physical examination, blood and urine tests, a review of drug side effects, and to receive the next week's supply of medications.

• Lumbar puncture (spinal tap): Patients have a lumbar puncture at study weeks 2, 4, and 6 to measure various brain chemicals and tau proteins in the cerebrospinal fluid (CSF), which bathes the brain and spinal cord. 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.

• Follow-up visit: Two weeks after completing the study medication, patients return to the clinic for a final evaluation, including a physical examination and blood and urine tests.

Clinical Trial 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 Design

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease

• NCT number: NCT00088387
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 2
• Start date: July 2004
• Completion date: March 2005