Clinical trial NCT00870311: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bipolar Disorder
Keywords: Lithium
Neuroprotection
Neurotrophic
bcl2
gsk3
pkc
MRI
myoinositol
MRS
Alzheimers Disease
Lead sponsor: Wayne State University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2009-03-27
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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)

Primary outcomes:
measure: Brain myo-inositol levels
timeFrame: 4 weeks
Secondary outcomes:
measure: Signal transduction pathway measures
timeFrame: 4 weeks
measure: Gene expression levels
timeFrame: 4 weeks
measure: Brain volume
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Wayne State University School of Medicine
state: Michigan
Study officials:
affiliation: Wayne State University, National Institute of Mental Health
name: Husseini K Manji, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University
name: Debra A Glitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wayne State University
name: Gregory J Moore, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.