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

Primary Purpose

Bipolar Disorder

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Lithium Carbonate

About this trial

This is an interventional basic science trial for Bipolar Disorder focused on measuring Lithium, Neuroprotection, Neurotrophic, bcl2, gsk3, pkc, MRI, myoinositol, MRS, Alzheimers Disease

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Wayne State University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Blinded Lithium

Arm Description

Bipolar Disorder patients

Outcomes

Primary Outcome Measures

Brain myo-inositol levels

Secondary Outcome Measures

Signal transduction pathway measures

Gene expression levels

Brain volume

Full Information

NCT ID

NCT00870311

First Posted

March 25, 2009

Last Updated

March 25, 2009

Sponsor

Wayne State University

Collaborators

National Institute of Mental Health (NIMH)

1. Study Identification

Unique Protocol Identification Number

NCT00870311

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2009

Overall Recruitment Status

Completed

Study Start Date

March 1996 (undefined)

Primary Completion Date

April 2004 (Actual)

Study Completion Date

April 2004 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Wayne State University

Collaborators

National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Bipolar Disorder

Keywords

Lithium, Neuroprotection, Neurotrophic, bcl2, gsk3, pkc, MRI, myoinositol, MRS, Alzheimers Disease

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

Participant

Allocation

Non-Randomized

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Blinded Lithium

Arm Type

Experimental

Arm Description

Bipolar Disorder patients

Intervention Type

Drug

Intervention Name(s)

Lithium Carbonate

Other Intervention Name(s)

Eskalith, Lithonate, Lithane, Lithotabs, Lithobid

Intervention Description

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.

Primary Outcome Measure Information:

Title

Brain myo-inositol levels

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

Signal transduction pathway measures

Time Frame

4 weeks

Title

Gene expression levels

Time Frame

4 weeks

Title

Brain volume

Time Frame

4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Husseini K Manji, MD

Organizational Affiliation

Wayne State University, National Institute of Mental Health

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Debra A Glitz, MD

Organizational Affiliation

Wayne State University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Gregory J Moore, MD, PhD

Organizational Affiliation

Wayne State University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Wayne State University School of Medicine

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

10511011

Citation

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. doi: 10.1097/00006842-199909000-00004.

Results Reference

result

PubMed Identifier

10588403

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):1902-8. doi: 10.1176/ajp.156.12.1902.

Results Reference

result

PubMed Identifier

10913502

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. 2000 Jul 1;48(1):1-8. doi: 10.1016/s0006-3223(00)00252-3.

Results Reference

result

PubMed Identifier

11072948

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. doi: 10.1016/s0140-6736(00)02793-8. Erratum In: Lancet 2000 Dec 16;356(9247):2104. Menji HK [corrected to Manji HK].

Results Reference

result

PubMed Identifier

19389332

Citation

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 Apr 21;70(5):699-705. doi: 10.4088/JCP.07m03745.

Results Reference

derived

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

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