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

Purpose

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.

Condition	Intervention	Phase
Bipolar Disorder	Drug: Lithium Carbonate	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Single Group Assignment Masking: Single Blind (Subject) Primary Purpose: Basic Science
Official Title:	Investigation of Lithium on Signal Transduction, Gene Expression and Brain Myo-Inositol Levels in Manic Patients

Resource links provided by NLM:

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Bipolar Disorder

Drug Information available for: Inositol Lithium carbonate Lithium citrate

U.S. FDA Resources

Further study details as provided by Wayne State University:

Primary Outcome Measures:

Brain myo-inositol levels [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Signal transduction pathway measures [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Gene expression levels [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Brain volume [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Enrollment:	28
Study Start Date:	March 1996
Study Completion Date:	April 2004
Primary Completion Date:	April 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Blinded Lithium Bipolar Disorder patients	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. Other Names: Eskalith Lithonate Lithane Lithotabs Lithobid

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00870311

Locations

United States, Michigan
Wayne State University School of Medicine
Detroit, Michigan, United States, 48201

Sponsors and Collaborators

Wayne State University

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:	Husseini K Manji, MD	Wayne State University, National Institute of Mental Health
Principal Investigator:	Debra A Glitz, MD	Wayne State University
Principal Investigator:	Gregory J Moore, MD, PhD	Wayne State University

More Information

Publications:

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.

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):1902-8.

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. 2000 Jul 1;48(1):1-8.

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].

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Moore GJ, Cortese BM, Glitz DA, Zajac-Benitez C, Quiroz JA, Uhde TW, Drevets WC, Manji HK. A longitudinal study of the effects of lithium treatment on prefrontal and subgenual prefrontal gray matter volume in treatment-responsive bipolar disorder patients. J Clin Psychiatry. 2009 May;70(5):699-705.

Responsible Party:	Husseini K. Manji, MD, F.R.C.P.C., Wayne State University and National Institute of Mental Health
ClinicalTrials.gov Identifier:	NCT00870311 History of Changes
Other Study ID Numbers:	H12-48-95, NIMH (MH159107)
Study First Received:	March 25, 2009
Last Updated:	March 25, 2009
Health Authority:	United States: Institutional Review Board

Keywords provided by Wayne State University:

Lithium
Neuroprotection
Neurotrophic
bcl2
gsk3

pkc
MRI
myoinositol
MRS
Alzheimers Disease

Additional relevant MeSH terms:

Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Inositol
Lithium
Lithium Carbonate
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

Pharmacologic Actions
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Antimanic Agents
Antidepressive Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 22, 2013