Investigation of Lithium on Signal Transduction, Gene Expression and Brain Myo-Inositol Levels in Manic Patients

Bipolar Disorder Clinical Trial

Official title:

Investigation of Lithium on Signal Transduction, Gene Expression and Brain Myo-Inositol Levels in Manic Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00870311
• Other study ID #: H12-48-95
• Secondary ID: NIMH (MH159107)
• Status: Completed
• Phase: Phase 4
• First received: March 25, 2009
• Last updated: March 25, 2009
• Start date: March 1996
• Est. completion date: April 2004

Study information

• Verified date: March 2009
• Source: Wayne State University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This study investigates the effects of Lithium treatment on signal transduction pathways, gene expression and brain neurochemistry and structure in patients with Bipolar disorder. It is hypothesized that specific changes in these markers will correlate with lithium treatment responsiveness.

Description:

This study investigates the effects of blinded lithium treatment longitudinally in patients with bipolar disorder. At baseline and at multiple time points following the initiation of lithium treatment over 4 or more weeks, measures of signal transduction pathways, gene expression and brain neurochemistry and structure were obtained. It is hypothesized that modulation of these measures will be predictive of lithium treatment responsiveness.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: April 2004
• Est. primary completion date: April 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Meet diagnostic criteria for Bipolar Mood Disorder determined by DSM-IV (SCID)

Exclusion Criteria:

• Meeting criteria for any other DSM-IV axis I disorder

• Psychoactive substance abuse or dependence within the past 1 year

• Medical conditions placing patients at increased risk for lithium treatment (including renal disease, hepatic disease, hematological disease)

• Devices/implants or conditions which preclude MRI investigation (including cardiac pacemaker/ICD, aneurysm clips, neurostimulator device, metallic fragments in or near the eye,claustrophobia)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Drug:
• Lithium Carbonate
300mg PO, three times daily with dose titrated to obtain a therapeutic plasma level of 0.8 to 1.2meq/L) over the first week of treatment. Total duration is a minimum of 3 weeks. Medication is dispensed in the form of blinded research capsules.

Locations

Country	Name	City	State
United States	Wayne State University School of Medicine	Detroit	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Wayne State University	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Chen G, Hasanat KA, Bebchuk JM, Moore GJ, Glitz D, Manji HK. Regulation of signal transduction pathways and gene expression by mood stabilizers and antidepressants. Psychosom Med. 1999 Sep-Oct;61(5):599-617. Review. — View Citation

Moore GJ, Bebchuk JM, Hasanat K, Chen G, Seraji-Bozorgzad N, Wilds IB, Faulk MW, Koch S, Glitz DA, Jolkovsky L, Manji HK. Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2's neurotrophic effects? Biol Psychiatry — View Citation

Moore GJ, Bebchuk JM, Parrish JK, Faulk MW, Arfken CL, Strahl-Bevacqua J, Manji HK. Temporal dissociation between lithium-induced changes in frontal lobe myo-inositol and clinical response in manic-depressive illness. Am J Psychiatry. 1999 Dec;156(12):190 — View Citation

Moore GJ, Bebchuk JM, Wilds IB, Chen G, Manji HK. Lithium-induced increase in human brain grey matter. Lancet. 2000 Oct 7;356(9237):1241-2. Erratum in: Lancet 2000 Dec 16;356(9247):2104. Menji HK [corrected to Manji HK]. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brain myo-inositol levels		4 weeks	No
Secondary	Signal transduction pathway measures		4 weeks	No
Secondary	Gene expression levels		4 weeks	No
Secondary	Brain volume		4 weeks	No