Disease-modifying Properties of Lithium in the Neurobiology of Alzheimer's Disease

Alzheimer Disease Clinical Trial

Official title:

Disease-modifying Properties of Lithium in the Neurobiology of Alzheimer's Disease: a Double-blind, Placebo-controlled Prevention Study in Elderly Patients With Mild Cognitive Impairment

Clinical Trial Details — Status: Unknown status

Administrative data

• NCT number: NCT01055392
• Other study ID #: OVForlenza-Lithium
• Secondary ID: 554535/2005-0
• Status: Unknown status
• Phase: Phase 2
• First received: January 22, 2010
• Last updated: January 22, 2010
• Start date: March 2007

Study information

• Verified date: December 2009
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Lithium salts have been used for the treatment of psychiatric disorders for over five decades, mostly as a mood-stabilizing drug. Recent evidence points to the inhibition of the enzyme glycogen synthase kinase-3beta (GSK3) as one of its mechanisms of action. The overactivity of this enzyme has been implicated in the pathogenesis of Alzheimer's disease (AD), given its involvement in mechanisms related to the hyperphosphorylation of Tau protein and the production of beta-amyloid peptide. These are key events leading respectively to the formation of neurofibrillary tangles and senile plaques, which are the neuropathological hallmarks of the disease. Several in vitro and animal studies have shown that the inhibition of GSK3 by lithium and other agents attenuates these pathological processes, reinforcing the notion that GSK3 is a likely target for future disease-modifying therapies for AD. Indeed, a recent study published by our group showed that chronic lithium use is associated with a decrement in the expected prevalence of dementia, in a sample of elderly individuals with bipolar disorder. To investigate this putative neuroprotective effect in a prospective way, the investigators started 24-month randomized, double-blinded controlled trial of lithium for the prevention of dementia in a sample of elderly individuals with amnestic mild cognitive impairment (MCI), a condition associated with increased risk for the development of AD. The clinical and biological outcomes of this trial include the attenuation of cognitive deficits, and the modification of certain biological markers of the disease (as measured in the cerebrospinal fluid, leukocytes and platelets). The objective of the present application is to enable the extension of this ongoing trial to an additional 2-year follow-up. A longer follow-up (48 months) will increase the statistical power to ascertain the primary outcome variables of this study, particularly the con-version from MCI to Alzheimer's disease. This will warrant a more consistent conclusion about the potential of lithium treatment in the prevention of dementia, in addition to a better evaluation of safety and tolerability profiles of the long-term use of lithium in older individuals.

Recruitment information / eligibility

• Status: Unknown status
• Enrollment: 80
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 80 Years

Eligibility

Inclusion Criteria:

• patients with amnestic mild cognitive impairment;

• age: 60 to 80 years-old;

Exclusion Criteria:

• sensory deficiencies that might preclude the administration of cognitive tests;

• active major psychiatry disorder;

• unstable clinical conditions such as cardiac insufficiency, uncontrolled diabetes mellitus, renal failure;

• previous use of lithium salts;

• concurrent participation in other clinical trial or intervention studies;

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Cognitive Impairment

Intervention

Drug:
• Lithium Carbonate
lithium carbonate tablets, 150 mg to 450 mg (target serum lithium level 0.25 mEq/L - 0.5 mEq/L), divided in two doses, two years.
• Placebo
Identical placebo tablets were administered twice-a-day for two years.

Locations

Country	Name	City	State
Brazil	Institute of Psychiatry, Faculty of Medicine - University of Sao Paulo	Sao Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	effect of lithium to delay progression of cognitive deficits in patients with amnestic MCI		two year
Secondary	effect of lithium on CSF levels of Total Tau, Phosphorylated Tau and Amyloid-beta42		one year
Secondary	the effect of lithium on the activity of GSK3ß in platelets and leukocytes drawn from peripheral blood.		one year