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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A: Other | Other | Open Label Study |
|
| B: Healthy Controls | No Intervention |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lamotrigine | Drug | Lamotrigine with dosage range from 25 mg to 200 mg per day. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean Glutamine to Creatine Ratio by Diagnosis at Baseline | Baseline | |
| Mean Glutamate to Creatine Ratio by Diagnosis at Baseline | Baseline | |
| Mean N-Acetyl Aspartate (NAA) to Creatine Ratio by Diagnosis at Baseline | 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. | Baseline |
| 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 | 8 Weeks |
| 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 | 8 weeks |
| 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 | 8 weeks |
| Association of MADRS Changes With Glutamate to Creatine Ratio Changes From Baseline to Follow-up |
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Inclusion Criteria (for Bipolar Subjects):
Exclusion Criteria (for Bipolar Subjects):
Inclusion Criteria (for Controls):
Exclusion Criteria (for Controls):
- Same criteria for the Bipolar Depressed group with the exception of the "first episode of mania" which is not applicable.
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| Name | Affiliation | Role |
|---|---|---|
| Brent P Forester, MD | Mclean Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| McLean Hospital | Belmont | Massachusetts | 02478 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | A: BPD Subjects | Open Label Study Lamotrigine : Lamotrigine with dosage range from 25 mg to 200 mg per day. |
| FG001 | B: Healthy Control | No Intervention |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Baseline scans were available for 37 participants, 23 BPD subjects and 14 for healthy controls. One participant had missing scan data, and twenty one participants with a BPD diagnosis had baseline MADRS scores available.
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| ID | Title | Description |
|---|---|---|
| BG000 | BPD Subjects | Open Label Study Lamotrigine : Lamotrigine with dosage range from 25 mg to 200 mg per day. |
| BG001 | Control Subjects | Age matched controls without BPD |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Mean Glutamine to Creatine Ratio by Diagnosis at Baseline | Baseline scans were available for 37 participants. One participant was missing scan data. | Posted | Mean | Standard Deviation | mean serum Glutamine to Creatine ratio | Baseline |
|
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Control Subjects | Age matched controls without BPD |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Loss of consciousness | Injury, poisoning and procedural complications | Subject fell off bicycle and lost consciousness. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rash | Skin and subcutaneous tissue disorders | Subject developed a rash, which was found to be unrelated by the subject's dermatologist. |
Limited data was available for associating changes in MADRS scores with metabolite changes (22 regions from 11 participants with BPD).
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Brent Forester | McLean Hospital | (617) 855-3622 | bforester@partners.org |
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| ID | Term |
|---|---|
| D001714 | Bipolar Disorder |
| ID | Term |
|---|---|
| D000068105 | Bipolar and Related Disorders |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000077213 | Lamotrigine |
| ID | Term |
|---|---|
| D014227 | Triazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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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. |
| 8 Weeks |
| 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. | 8 weeks |
| 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. | 8 weeks |
| 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. | Baseline |
| Means of MADRS Scores at 8 Weeks | The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed. | 8 Weeks |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Participants |
|
|
| Primary | Mean Glutamate to Creatine Ratio by Diagnosis at Baseline | Baseline scans were available for 37 participants. One participant was missing scan data. | Posted | Mean | Standard Deviation | mean serum Glutamate to Creatine ratio | Baseline |
|
|
|
| Primary | Mean N-Acetyl Aspartate (NAA) to Creatine Ratio by Diagnosis at Baseline | Baseline scans were available for 37 participants. One participant was missing scan data. | Posted | Mean | Standard Deviation | Mean NAA to creatine ratio | Baseline |
|
|
|
| Primary | 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. | Association between depression symptom severity and metabolite ratios were only conducted in the depressed group, because there should be no change in MADRS score for non-depressed control subjects who received no treatment. | Posted | Least Squares Mean | 95% Confidence Interval | Glu:Cr/+10 MADRS | Baseline |
|
|
|
| Primary | 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 | Posted | Least Squares Mean | 95% Confidence Interval | serum Glutamate to Creatine ratio | 8 Weeks |
|
|
|
| Primary | 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 | Posted | Least Squares Mean | 95% Confidence Interval | serum Glutamine to Creatine ratio | 8 weeks |
|
|
|
| Primary | 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 | Posted | Least Squares Mean | 95% Confidence Interval | NAA to creatine ratio | 8 weeks |
|
|
|
| Primary | 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. | Association between depression symptom severity and metabolite ratios were only conducted in the depressed group, because there should be no change in MADRS score for non-depressed control subjects who received no treatment. | Posted | Least Squares Mean | 95% Confidence Interval | Glu:Cr/-10 MADRS | 8 Weeks |
|
|
|
| Primary | 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. | Association between depression symptom severity and metabolite ratios were only conducted in the depressed group, because there should be no change in MADRS score for non-depressed control subjects who received no treatment. | Posted | Least Squares Mean | 95% Confidence Interval | Gln:Cr/-10 MADRS Score | 8 weeks |
|
|
|
| Primary | 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. | Association between depression symptom severity and metabolite ratios were only conducted in the depressed group, because there should be no change in MADRS score for non-depressed control subjects who received no treatment. | Posted | Least Squares Mean | 95% Confidence Interval | NAA:Cr/-10 MADRS | 8 weeks |
|
|
|
| Primary | 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. | MADRS scores were available for 27 eligible bipolar subjects and 14 eligible controls. | Posted | Mean | Standard Deviation | units on a scale | Baseline |
|
|
|
| Primary | Means of MADRS Scores at 8 Weeks | The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed. | MADRS scores were available for 16 bipolar subjects who completed the protocol and 8 healthy controls. | Posted | Mean | Standard Deviation | units on a scale | 8 Weeks |
|
|
|
| 0 |
| 24 |
| 0 |
| 24 |
| EG001 | BPD Subjects | 2 | 45 | 14 | 45 |
|
| Mania | Psychiatric disorders | Subject was hospitalized due to mania |
|
|
| Rash | Skin and subcutaneous tissue disorders | Subject developed a rash after taking second dose. |
|
| Blister | Skin and subcutaneous tissue disorders | Subject reported developing a blister on the hand. |
|
| mania | Psychiatric disorders | Subject entered a manic state, with decreased sleep, pressured speech, and delusions. |
|
| Blurry Vision | Eye disorders | Subject reported blurry vision |
|
| Insomnia | Psychiatric disorders | Four subjects reported sleep disturbances. |
|
| Decreased balance | General disorders | Three subjects reported feeling unbalanced or dizzy. |
|
| Stomach upset | Gastrointestinal disorders | Two subject reported gastrointestinal problems including upset stomach and indigestion. |
|
| Irritability | Psychiatric disorders | One subject experienced increased irritability |
|
| Headache | General disorders | Two subjects reported mild headaches. |
|
| Runny Nose | Respiratory, thoracic and mediastinal disorders | One subject reported a mild runny nose. |
|
| Weight gain | Metabolism and nutrition disorders | A subject reported gaining one pound. |
|
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