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Lamotrigine Therapy in Geriatric Bipolar Depression

Primary Purpose

Bipolar Depression

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Lamotrigine
Sponsored by
Mclean Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Bipolar Depression focused on measuring Bipolar depression, Elderly, Lamotrigine, Brain energy metabolism

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria (for Bipolar Subjects):

  • 60 years or older
  • Meet DSM-IV diagnostic criteria for Bipolar Disorder, Current Episode Depressed
  • First episode of mania before the age of 50 (early-onset bipolar disorder)
  • Montgomery-Asberg Depression Rating Scale (MADRS) Score of greater or equal to 20.
  • Young Mania Rating Scale (YMRS) of less than or equal to 6.
  • Able to provide informed consent
  • Must speak English
  • Must be able to visit McLean Hospital for the screening visit and six study visits during the 8-week duration of the study.
  • Subjects may be taking other medications for bipolar depression including antidepressants, mood stabilizers and antipsychotic mediations prior to lamotrigine therapy, but may not have any dosage adjustments of these medications in the week before lamotrigine is added.

Exclusion Criteria (for Bipolar Subjects):

  • Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease.
  • History of seizure disorder
  • History or current diagnosis of the following psychiatric illnesses: any organic mental disorder (including dementia), schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorder not otherwise specified, unipolar major depressive disorder, patients with substance dependence disorders, including alcohol, active within the last 12 months.
  • First episode of mania after the age of 50 (to exclude late-onset bipolar disorder)
  • History of multiple adverse drug reactions or allergy to the study drugs.
  • Use of medications that are excluded in this study (benzodiazepines, barbiturates; however, the use of non-benzodiazepine sedative hypnotics (such as zolpidem (Ambien)) may be used as needed except within 48 hours of the MRI scan)
  • Any of the exclusion criteria mentioned in the MRI risks section below

Inclusion Criteria (for Controls):

  • 60 years or older
  • Able to provide informed consent
  • Must speak English
  • Women entering this study must be post-menopausal

Exclusion Criteria (for Controls):

- Same criteria for the Bipolar Depressed group with the exception of the "first episode of mania" which is not applicable.

Sites / Locations

  • McLean Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

No Intervention

Arm Label

A: Other

B: Healthy Controls

Arm Description

Open Label Study

Outcomes

Primary Outcome Measures

Mean Glutamine to Creatine Ratio by Diagnosis at Baseline
Mean Glutamate to Creatine Ratio by Diagnosis at Baseline
Mean N-Acetyl Aspartate (NAA) to Creatine Ratio by Diagnosis at Baseline
Associations Between Depression Symptom Severity and Glutamate to Creatine Ratio at Baseline
Estimated changes in least squares mean in the metabolite ratio per 10-point increase in MADRS score. The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed. Estimate was from linear regression models controlling for age and sex. The change is across regions, parieto-occipital and anterior cingulate cortex.
Estimated Change in Least Squares Mean in Glutamate to Creatine Ratio Between Baseline and Follow-up
Follow-up Least Squares Mean - Baseline Least Squares Mean
Estimated Change in Least Squares Mean in the Glutamine to Creatine Ratio Between Baseline and Follow-up
Follow-up Least Squares Mean - Baseline Least Squares Mean
Estimated Change in Least Squares Mean in the NAA to Creatine Ratio Between Baseline and Follow-up
Follow-up Least Squares Mean - Baseline Least Squares Mean
Association of MADRS Changes With Glutamate to Creatine Ratio Changes From Baseline to Follow-up
Estimated least squares mean metabolite ratio changes with a 10-point decrease in MADRS score. The MADRS minimum score is 0 and maximum is 60, with 60 being the most depressed score. Estimate was from linear regression models controlling for age and sex. The change is across regions, parieto-occipital and anterior cingulate cortex.
Associations of MADRS Changes With Glutamine to Creatine Ratio Changes From Baseline to Follow-up
Estimated least squares mean metabolite ratio changes with a 10-point decrease in MADRS score. MADRS minimum score is 0 and maximum is 60, with 60 being most depressed. Estimate was from linear regression models controlling for age and sex. The change is across regions, parieto-occipital and anterior cingulate cortex.
Associations of MADRS Changes With NAA to Creatine Ratio Changes From Baseline to Follow-up
Estimated least squares mean metabolite ratio changes with a 10-point decrease in MADRS score. MADRS minimum score is 0 and maximum is 60, with 60 being most depressed. Estimate was from linear regression models controlling for age and sex. The change is across regions, parieto-occipital and anterior cingulate cortex.
Mean Montgomery Asberg Depression Rating Scale (MADRS) Score at Baseline
The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed.
Means of MADRS Scores at 8 Weeks
The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed.

Secondary Outcome Measures

Full Information

First Posted
July 18, 2008
Last Updated
January 30, 2017
Sponsor
Mclean Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT00720473
Brief Title
Lamotrigine Therapy in Geriatric Bipolar Depression
Official Title
Lamotrigine Therapy in the Treatment of Geriatric Bipolar Depression: An Evaluation of Markers of Cerebral Energy Metabolism
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
April 2006 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mclean Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
We propose to study the efficacy and tolerability of lamotrigine in the treatment of older adults with bipolar depression and to compare measures of brain energy metabolism between older subjects with bipolar depression and healthy age-matched controls in order to better understand treatment response in geriatric bipolar depression.
Detailed Description
We will use MRI techniques and neuropsychological testing to investigate potential markers of treatment response in elderly bipolar depressed patients receiving lamotrigine and age-matched, non-depressed controls. We intend to test these hypotheses: At least 50% of older subjects with bipolar depression will respond treatment with lamotrigine as evidenced by a 50% reduction on the Montgomery Asberg Rating Scale (MADRS). In addition, treatment with lamotrigine will be safe and well tolerated as evidenced by a drop-out rate of less than 10% due to adverse effects. Compared with healthy age-matched, non-demented, non-depressed controls, subjects with geriatric bipolar depression will demonstrate abnormalities in cerebral energy metabolism as assessed by elevated levels of glutamate and lactate, and decreased levels of NAA, using 1H MRS at 4T. Successful treatment with lamotrigine in geriatric bipolar depression will result in decreases in lactate and glutamate, and elevations in NAA. Baseline measures of executive functioning and information processing speed (measured by performance on the Wisconsin Card Sorting Test (WCST), Trails A and B and Stroop tests) will be impaired in subjects with geriatric bipolar depression compared with healthy controls. These measures will improve with successful treatment with lamotrigine and correlate with improvements in markers of cerebral energy metabolism (lactate, glutamate, NAA).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Depression
Keywords
Bipolar depression, Elderly, Lamotrigine, Brain energy metabolism

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
69 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A: Other
Arm Type
Other
Arm Description
Open Label Study
Arm Title
B: Healthy Controls
Arm Type
No Intervention
Intervention Type
Drug
Intervention Name(s)
Lamotrigine
Other Intervention Name(s)
Lamictal
Intervention Description
Lamotrigine with dosage range from 25 mg to 200 mg per day.
Primary Outcome Measure Information:
Title
Mean Glutamine to Creatine Ratio by Diagnosis at Baseline
Time Frame
Baseline
Title
Mean Glutamate to Creatine Ratio by Diagnosis at Baseline
Time Frame
Baseline
Title
Mean N-Acetyl Aspartate (NAA) to Creatine Ratio by Diagnosis at Baseline
Time Frame
Baseline
Title
Associations Between Depression Symptom Severity and Glutamate to Creatine Ratio at Baseline
Description
Estimated changes in least squares mean in the metabolite ratio per 10-point increase in MADRS score. The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed. Estimate was from linear regression models controlling for age and sex. The change is across regions, parieto-occipital and anterior cingulate cortex.
Time Frame
Baseline
Title
Estimated Change in Least Squares Mean in Glutamate to Creatine Ratio Between Baseline and Follow-up
Description
Follow-up Least Squares Mean - Baseline Least Squares Mean
Time Frame
8 Weeks
Title
Estimated Change in Least Squares Mean in the Glutamine to Creatine Ratio Between Baseline and Follow-up
Description
Follow-up Least Squares Mean - Baseline Least Squares Mean
Time Frame
8 weeks
Title
Estimated Change in Least Squares Mean in the NAA to Creatine Ratio Between Baseline and Follow-up
Description
Follow-up Least Squares Mean - Baseline Least Squares Mean
Time Frame
8 weeks
Title
Association of MADRS Changes With Glutamate to Creatine Ratio Changes From Baseline to Follow-up
Description
Estimated least squares mean metabolite ratio changes with a 10-point decrease in MADRS score. The MADRS minimum score is 0 and maximum is 60, with 60 being the most depressed score. Estimate was from linear regression models controlling for age and sex. The change is across regions, parieto-occipital and anterior cingulate cortex.
Time Frame
8 Weeks
Title
Associations of MADRS Changes With Glutamine to Creatine Ratio Changes From Baseline to Follow-up
Description
Estimated least squares mean metabolite ratio changes with a 10-point decrease in MADRS score. MADRS minimum score is 0 and maximum is 60, with 60 being most depressed. Estimate was from linear regression models controlling for age and sex. The change is across regions, parieto-occipital and anterior cingulate cortex.
Time Frame
8 weeks
Title
Associations of MADRS Changes With NAA to Creatine Ratio Changes From Baseline to Follow-up
Description
Estimated least squares mean metabolite ratio changes with a 10-point decrease in MADRS score. MADRS minimum score is 0 and maximum is 60, with 60 being most depressed. Estimate was from linear regression models controlling for age and sex. The change is across regions, parieto-occipital and anterior cingulate cortex.
Time Frame
8 weeks
Title
Mean Montgomery Asberg Depression Rating Scale (MADRS) Score at Baseline
Description
The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed.
Time Frame
Baseline
Title
Means of MADRS Scores at 8 Weeks
Description
The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed.
Time Frame
8 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria (for Bipolar Subjects): 60 years or older Meet DSM-IV diagnostic criteria for Bipolar Disorder, Current Episode Depressed First episode of mania before the age of 50 (early-onset bipolar disorder) Montgomery-Asberg Depression Rating Scale (MADRS) Score of greater or equal to 20. Young Mania Rating Scale (YMRS) of less than or equal to 6. Able to provide informed consent Must speak English Must be able to visit McLean Hospital for the screening visit and six study visits during the 8-week duration of the study. Subjects may be taking other medications for bipolar depression including antidepressants, mood stabilizers and antipsychotic mediations prior to lamotrigine therapy, but may not have any dosage adjustments of these medications in the week before lamotrigine is added. Exclusion Criteria (for Bipolar Subjects): Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease. History of seizure disorder History or current diagnosis of the following psychiatric illnesses: any organic mental disorder (including dementia), schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorder not otherwise specified, unipolar major depressive disorder, patients with substance dependence disorders, including alcohol, active within the last 12 months. First episode of mania after the age of 50 (to exclude late-onset bipolar disorder) History of multiple adverse drug reactions or allergy to the study drugs. Use of medications that are excluded in this study (benzodiazepines, barbiturates; however, the use of non-benzodiazepine sedative hypnotics (such as zolpidem (Ambien)) may be used as needed except within 48 hours of the MRI scan) Any of the exclusion criteria mentioned in the MRI risks section below Inclusion Criteria (for Controls): 60 years or older Able to provide informed consent Must speak English Women entering this study must be post-menopausal Exclusion Criteria (for Controls): - Same criteria for the Bipolar Depressed group with the exception of the "first episode of mania" which is not applicable.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brent P Forester, MD
Organizational Affiliation
Mclean Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
McLean Hospital
City
Belmont
State/Province
Massachusetts
ZIP/Postal Code
02478
Country
United States

12. IPD Sharing Statement

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Lamotrigine Therapy in Geriatric Bipolar Depression

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