Bipolar DepressionNCT00720473

Lamotrigine Therapy in Geriatric Bipolar Depression

A study testing Lamotrigine in people with Bipolar Depression, run by Mclean Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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… Read more about this study

Who is it for?: Ages 60 years and olderHealthy volunteers can take part
Conditions the study is for: Bipolar Depression
What is being tested?: Lamotrigine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 69 participants
Where: 1 siteUnited States
Study dates: Apr 2006to Dec 2011
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 60 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Show all 13Show fewer

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

McLean Hospital
Belmont, Massachusetts, 02478

Other trials in United States

About this study

Official title: Lamotrigine Therapy in the Treatment of Geriatric Bipolar Depression: An Evaluation of Markers of Cerebral Energy Metabolism

Read the 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).

Conditions: Bipolar Depression
Being tested: Lamotrigine
Keywords: Bipolar depression, Elderly, Lamotrigine, Brain energy metabolism
Medical subject headings: Bipolar Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LamotrigineDrug
Also called Lamictal
Lamotrigine with dosage range from 25 mg to 200 mg per day.

Study groups in NCT00720473
Study group	Role	What they receive
A: Other	Other	Open Label Study Receives: Drug: Lamotrigine
B: Healthy Controls	No intervention	Not described

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Glutamine to Creatine Ratio by Diagnosis at Baseline
Measured: Baseline
Mean Glutamate to Creatine Ratio by Diagnosis at Baseline
Measured: Baseline
Mean N-Acetyl Aspartate (NAA) to Creatine Ratio by Diagnosis at Baseline
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 8 weeks
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 8 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2006Dec 2011

First posted22 Jul 2008 (estimated)
Study startApr 2006
Primary completionJul 2011
Study completionDec 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Bipolar DepressionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 69 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00720473
Sponsor's protocol ID: 2005-P-002493
Status last verified: Jan 2017
First submitted: 18 Jul 2008
Last updated: 1 Feb 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Bipolar Depression trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Lamotrigine Therapy in the Treatment of Geriatric Bipolar Depression: An Evaluation of Markers of Cerebral Energy Metabolism
ClinicalTrials.gov ID: NCT00720473
Acronym / sponsor ID: 2005-P-002493
Conditions: Bipolar Depression
Keywords: Bipolar depression, Elderly, Lamotrigine, Brain energy metabolism
Study type: Interventional
Recruitment status: Completed
Enrolment: 69 participants (actual)
Lead sponsor: Mclean HospitalUniversity, hospital or other
Study start: Apr 2006
Primary completion: Jul 2011 (actual)
Study completion: Dec 2011 (actual)
First posted: 22 Jul 2008 (estimated)
Results: Posted 21 Jul 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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).

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
A: Other	Other	Drug: LamotrigineOpen Label Study
B: Healthy Controls	No intervention	–

Who may qualify

Ages: 60 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

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.

Key exclusion criteria (8 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LamotrigineAlso: LamictalLamotrigine with dosage range from 25 mg to 200 mg per day.	Drug	A: Other

Primary outcome

Mean Glutamine to Creatine Ratio by Diagnosis at Baseline
Time frame: Baseline
Mean Glutamate to Creatine Ratio by Diagnosis at Baseline
Time frame: Baseline
Mean N-Acetyl Aspartate (NAA) to Creatine Ratio by Diagnosis at Baseline
Time frame: Baseline
Associations Between Depression Symptom Severity and Glutamate to Creatine Ratio at Baseline
Time frame: 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
Time frame: 8 Weeks
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
Time frame: 8 weeks
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
Time frame: 8 weeks
Follow-up Least Squares Mean - Baseline Least Squares Mean
Association of MADRS Changes With Glutamate to Creatine Ratio Changes From Baseline to Follow-up
Time frame: 8 Weeks
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
Time frame: 8 weeks
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
Time frame: 8 weeks
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
Time frame: 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
Time frame: 8 Weeks
The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed.

Results and safety

Results posted to the registry on 21 Jul 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
A: BPD Subjects	45	15
B: Healthy Control	24	16

Primary outcome: Mean Glutamine to Creatine Ratio by Diagnosis at Baseline

Time frame: Baseline. Mean (Standard Deviation). Unit: mean serum Glutamine to Creatine ratio

Measure	BPD Subjects n = 22	Control Subjects n = 14
Value	.34 (.12)	.36 (.18)

Population analysed: Baseline scans were available for 37 participants. One participant was missing scan data.

Primary outcome: Mean Glutamate to Creatine Ratio by Diagnosis at Baseline

Time frame: Baseline. Mean (Standard Deviation). Unit: mean serum Glutamate to Creatine ratio

Measure	BPD Subjects n = 22	Control Subjects n = 14
Value	.96 (.29)	.85 (.25)

Population analysed: Baseline scans were available for 37 participants. One participant was missing scan data.

Primary outcome: Mean N-Acetyl Aspartate (NAA) to Creatine Ratio by Diagnosis at Baseline

Time frame: Baseline. Mean (Standard Deviation). Unit: Mean NAA to creatine ratio

Measure	BPD Subjects n = 22	Control Subjects n = 14
Value	0.97 (0.14)	0.84 (0.22)

Population analysed: Baseline scans were available for 37 participants. One participant was missing scan data.

Primary outcome: Associations Between Depression Symptom Severity and Glutamate to Creatine Ratio at Baseline

Time frame: Baseline. Least squares mean (95% Confidence Interval). Unit: Glu:Cr/+10 MADRS

Measure	A: Other n = 21
Value	0.18 (-0.02 to 0.38)

Population analysed: 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.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Control Subjects	0 of 24 (0%)	0 of 24 (0%)	Not reported
BPD Subjects	2 of 45 (4.4%)	14 of 45 (31.1%)	Not reported

Limitations and caveats (from the sponsor): Limited data was available for associating changes in MADRS scores with metabolite changes (22 regions from 11 participants with BPD).

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Bipolar Depression

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Brent P Forester, MD principal investigator

Mclean Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Lamotrigine in people with Bipolar Depression, run by Mclean Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Glutamine to Creatine Ratio by Diagnosis at Baseline (time frame: Baseline). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00720473.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2017.