PET and MRI Brain Imaging of Bipolar Disorder

NCT01880957 | Completed Results

• 2 other identifiers: 2012-1826-F7R01MH090276-03
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aims of this study are to:

1. 1.Quantify serotonin transporter (5-HTT) binding potential (BP) in vivo in bipolar disorder patients (BPD) during a major depressive episode (MDE).
2. 2.Assess the effect of lithium treatment of bipolar disorder on 5-HTT.
3. 3.Assess the effect of lithium treatment of bipolar disorder on 5-HT1A BP.
4. 4.Assess the effect of lamotrigine treatment of bipolar disorder on 5-HTT and 5-HT1A BP.
5. 5.Assess the effect of lithium treatment of unipolar depression on 5-HTT BP.

Conditions

Bipolar Disorder; Bipolar Depression; Unipolar Depression

Keywords

bipolar disorder; bipolar depression; serotonin transporter; serotonin receptors; binding potential; brain imaging; unipolar depression

Outcome Measures

Primary Outcomes (2)

• Post-Lithium Treatment Hamilton Depression Rating Scale (HDRS)

  Patients will have a Hamilton Depression Rating Scale-24 (HDRS) score obtained at baseline. Minimum score 0, maximum possible score 75; the higher the score on the scale, the more severe the degree of depression. Participants must have an HDRS score of at least 15 to be eligible. After eight weeks of medication treatment, the HDRS score will be reevaluated with the HDRS-24 (and rescanned with PET and MRI). Participants who have a 50% or greater decrease in their HDRS-24 score will be considered responders (to Lithium treatment).

  8 weeks

• Prediction of Treatment Response

  Outcome measures were generated following LASSO linear regression analysis using pretreament HDRS-24 AND.. 1. pre-treatment 5-HTT OR 2. pretreatment 5-HT1A OR 3. the combination of both 5-HTT and 5-HT1A binding potential * to predict post-treatment response defined by a dichotomous remission status variable (remitter vs. non-remitter, where remitter is defined a priori by HDRS-24 \<10 post-treatment and a reduction of greater than or equal to 50% in HDRS-24 pre-to-post treatment). Outcome measure is reported as percent accuracy, sensitivity, or specificity in predicting remitter status outcomes.

  8 Weeks

Secondary Outcomes (3)

• Group Differences in 5-HTT Binding Potential

  8 Weeks

• Group Differences in 5-HT1A Binding Potential

  8 Weeks

• Relationship Between Change in 5-HTT or 5-HT1A Binding Potential Pre- to Post Treatment and Lithium Treatment Response

  8 weeks

Study Arms (2)

Lithium

OTHER

Patients in this condition will receive lithium administered as follows: Day 1, 2 and 3, 300 mg bid; Days 4-7 lithium 300 qam and 600 qhs. Lithium level will be checked as close to Day 7 as possible and titrated to a therapeutic plasma level of 0.8-1.2 mEq/l. Subjects will not undergo lithium monotherapy if they have a documented history of at least two failed trials of lithium of at least 4 weeks duration with therapeutic blood levels for a major depressive episode

Drug: Lithium

Lamotrigine

OTHER

Patients who have not respond to adequate prior lithium treatment while depressed, or who refuse lithium, will be given lamotrigine. Lamotrigine will be started at 25 mg bid and increased to 50 mg bid after 2 weeks and again increased to 100 mg bid after an additional 2 weeks.

Drug: Lamotrigine

Interventions

Lithium DRUG

Also known as: lithium carbonate

Lithium

Lamotrigine DRUG

Also known as: Lamictal

Lamotrigine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Bipolar patients suffering from a major depressive episode currently or recently (in the month prior to scanning). Patients on psychiatric medication will have failed their current regimen for the treatment of their depression: they will meet criteria for depression, be seeking treatment for it, and have been on an adequate dose of antidepressant or mood stabilizer (as defined by the Antidepressant Treatment Form-see Oquendo et al., 2003) for 4 weeks or more.
• Of sufficient severity to score at least 15 on the first 17 items of the Hamilton Depression Rating Scale or a score of 10 to 14 on the first 17 items of the Hamilton Depression Scale in conjunction with a score of at least 29 on the Beck Depression Inventory.
• Age range 18-65 years.
• Off all psychotropic and other types of drugs likely to interact with serotonin transporters and 5-HT1A receptors for at least 21 days. Allowed short-acting benzodiazepines for distressing anxiety or insomnia (up to 24 hours prior to each PET scan). Patients will be off neuroleptics for 3 weeks and off fluoxetine for 6 weeks prior to study. Off serotonin depleting drugs such as reserpine for 3 months. Patient will also be off anti-coagulant/anti-platelet treatment such as coumadin, with the exception of aspirin for 10 days.
• Willing to travel for PET scanning

You may not qualify if:

• Other major psychiatric disorders such as schizophrenia, schizoaffective illness; current drug or alcohol abuse (within past 2 months), or drug or alcohol dependence \<6mos ago; anorexia nervosa or bulimia nervosa in the past year; IV drug use or ecstasy use more than two times.
• A first-degree family history of schizophrenia if the subject is less than 33 years old (mean age of onset for schizophrenia plus two standard deviations).
• Significant active physical illness particularly those that may affect the brain or serotonergic system including blood dyscrasias lymphomas, hypersplenism, endocrinopathies, renal failure or chronic obstructive lung disease, autonomic neuropathies, peripheral vascular disease, diabetes, low hemoglobin and malignancy, significant anemic disease or blood loss and the lab parameters platelet count \< 80,000.
• Lacks capacity to consent.
• Actively suicidal-begins expressing a plan for suicide during the washout phase or develop suicidal ideation that warrants admission or requires medication or treatment intervention.
• Electroconvulsive therapy (ECT) within the past 6 months.
• Pregnancy, currently lactating; planning to conceive during the course of study participation or abortion in the past two months.
• Metal implants, pacemaker or metal prostheses or orthodontic appliances, the presence of shrapnel
• Current, past or anticipated exposure to radiation, that may include: being badged for radiation exposure in the workplace, participation in nuclear medicine procedures, including research protocols in the last year.
• A neurological disease or loss of consciousness for more than a few minutes
• Medicinal Patch (participants will be asked to remove before MRI)
• Patients who are responding satisfactorily to psychiatric medications, because they will not be washed-out for purposes of this study
• A documented history of a lack of response to a trial of adequate dose and duration of both lithium and lamotrigine defined as minimal clinical response to lamotrigine 200 mgs for at least 4 weeks or lithium serum levels of at least 0.8 (or dose \>= 900 mgs) for at least 4 weeks.
• Patient is unlikely to be able to tolerate medication washout
• Claustrophobia

Sponsors & Collaborators

• Stony Brook University: lead
• National Institute of Mental Health (NIMH): collaborator
• The Dana Foundation: collaborator

Study Sites (1)

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

Location

Related Publications (1)

• Ananth M, Bartlett EA, DeLorenzo C, Lin X, Kunkel L, Vadhan NP, Perlman G, Godstrey M, Holzmacher D, Ogden RT, Parsey RV, Huang C. Prediction of lithium treatment response in bipolar depression using 5-HTT and 5-HT1A PET. Eur J Nucl Med Mol Imaging. 2020 Sep;47(10):2417-2428. doi: 10.1007/s00259-020-04681-6. Epub 2020 Feb 13.

  PMID: 32055965 DERIVED

MeSH Terms

Conditions

Bipolar Disorder; Depressive Disorder

Interventions

Lithium; Lithium Carbonate; Lamotrigine

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals; Carbonates; Alkalies; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds; Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Limitations include: 1. a small sample size, which precludes investigation into interaction factors (e.g. sex/BPD subtype); 2. a short washout duration (3 weeks for ethical reasons), which may not be sufficient to abate treatment effects; 3. scans for both patients and controls conducted across multiple sites, though, importantly, all pre- and post-treatment scans within-participant were conducted at the same site.

Results Point of Contact

• Title: Dr. Christine DeLorenzo
• Organization: Stony Brook University

Christine.Delorenzo@stonybrookmedicine.edu

(631) 638-1523

Study Officials

• Ramin Parsey, MD, PhD

  Stony Brook University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chair of the Department of Psychiatry and Director of Positron Emission Tomography (PET) Research

Study Record Dates

• First Submitted: June 17, 2013
• First Posted: June 19, 2013
• Study Start: November 8, 2011
• Primary Completion: June 23, 2017
• Study Completion: June 23, 2017
• Last Updated: July 20, 2022
• Results First Posted: June 29, 2022

Record last verified: 2022-07

Locations

US (1)