Bipolar Depression Before and After Lamotrigine Treatment

NCT01042496 | Completed Phase 3 Results DMC

• 2 other identifiers: 09-004163R01MH079261-01A2
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

This study compared glutamate and other neurometabolites measured by proton magnetic resonance spectroscopy (1H-MRS) in bipolar I and II patients currently depressed with age-matched healthy controls. The study will also compare 1H-MRS of bipolar I and II patients before and after taking a 12-week course of lamotrigine. The goal of this study was to better understand the neurobiology of bipolar depression and how lamotrigine may therapeutically impact brain function and mood response. The hypothesis was that in comparison to non-remission participants, bipolar participants who achieve remission (defined as a Montgomery Asberg Depression Rating Scale (MADRS) score \<12 at week 12) associated with lamotrigine monotherapy will exhibit a greater decrease in glutamate (Glu) and an increase in N-acetyl aspartate (NAA), reported as a cerebrospinal fluid (CSF)-corrected absolute concentration percent change from baseline to endpoint in anterior cingulate (AC) and dorsolateral prefrontal cortex (DLPFC).

Conditions

Bipolar Depression

Keywords

Bipolar; depression

Outcome Measures

Primary Outcomes (1)

• Mean Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group

  The MADRS is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed). A score of less than 12 is considered clinical remission of depression.

  baseline, 12 weeks

Secondary Outcomes (4)

• Glutamate+Glutamine (GLX) Measured in Mid Anterior Cingulate Cortex (MACC) & Left Dorsal Lateral Prefrontal Cortex (LDLPC) Using Long TE PRESS MRS Technique at Baseline for Both Groups; After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group

  baseline, after 12 weeks

• N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders

  baseline, 12 weeks

• Mean Glutamate (GLU) Measured in the MACC and LDLPC Using the ProFit MRS Technique at Baseline for Both Groups, After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group

  baseline, 12 weeks

• Glutamine/Glutamate Ratio Measured in the LDLPC at Baseline Using the ProFit Magnetic Resonance Spectroscopy (MRS) Technique

  baseline

Study Arms (2)

Bipolar Group

ACTIVE COMPARATOR

Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC) before and after treatment with Lamotrigine.

Drug: Lamotrigine; Procedure: 1H-MR

Control Group

ACTIVE COMPARATOR

Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).

Procedure: 1H-MR

Interventions

Lamotrigine DRUG

12 week open trial: 25mg/day for 2 weeks, 50mg/day for 2 weeks, 100mg/day for 2 weeks, 200mg/day for 6 weeks. Flexible titration for early response and/or side effects.

Also known as: Lamictal®

Bipolar Group

1H-MR PROCEDURE

Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).

Bipolar Group; Control Group

Eligibility Criteria

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

You may qualify if:

• Diagnosis of Bipolar Type I or II disorder depress phase (SCID confirmed)
• Moderate depression as confirmed by Montgomery Asberg Depression Rating Scale greater than or equal to 20
• Negative urine toxicology screen
• Negative urine pregnancy test
• No clinically significant lab abnormalities for complete blood count (CBC), Thyroid stimulating hormone (TSH), Sodium (Na+), Potassium (K+), Chlorine (Cl-), Carbon dioxide (CO2), creatinine (CREA), blood urea nitrogen (BUN), Glucose, hepatic panel.

You may not qualify if:

• Inability to provide informed consent
• Any current Axis I diagnosis other than anxiety disorders needing concurrent antidepressant therapy
• History of active substance abuse/dependence within the last 3 months
• History of claustrophobia
• History of adverse reaction to Lamotrigine
• Fluoxetine and decanoate antipsychotic therapy
• Unwilling or unable to taper current sub-optimal psychotropic medications other than a stable dosage of Lithium, Depakote, or an Atypical Antipsychotic approved by study personnel
• Unstable active medical illness
• Pregnancy or breast-feeding
• Male/ Female not practicing a reliable form of birth control (condom, Intrauterine Device (IUD), depo injection)
• Female wishing to commence oral contraceptive therapy within 3 months of enrollment date (stable oral contraceptive therapy exception)
• Active suicidal ideation with plan
• History of major head trauma with loss of consciousness \> 5 minutes or skull fracture
• History of previous neurological event (epilepsy, stroke, transient ischemic attack)
• Implanted metal objects (i.e., pacemakers, aneurysm clips, metal prostheses, joints, rods)

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Bipolar Disorder; Depression

Interventions

Lamotrigine

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Mark A. Frye
• Organization: Mayo Clinic

MFrye@mayo.edu

507-284-6213

Study Officials

• Mark Frye, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: January 4, 2010
• First Posted: January 5, 2010
• Study Start: December 1, 2009
• Primary Completion: September 1, 2014
• Study Completion: October 1, 2014
• Last Updated: February 8, 2016
• Results First Posted: January 12, 2016

Record last verified: 2016-01

Locations

US (1)