Trial Outcomes & Findings for Lamotrigine Therapy in Geriatric Bipolar Depression (NCT NCT00720473)

NCT ID: NCT00720473

Last Updated: 2017-02-01

Results Overview

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 69 participants
• Primary outcome timeframe: Baseline
• Results posted on: 2017-02-01

Participant Flow

Participant milestones

Measure	A: BPD Subjects Open Label Study Lamotrigine : Lamotrigine with dosage range from 25 mg to 200 mg per day.	B: Healthy Control No Intervention
Overall Study STARTED	45	24
Overall Study COMPLETED	15	16
Overall Study NOT COMPLETED	30	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Lamotrigine Therapy in Geriatric Bipolar Depression

Baseline characteristics by cohort

Measure	BPD Subjects n=23 Participants Open Label Study Lamotrigine : Lamotrigine with dosage range from 25 mg to 200 mg per day.	Control Subjects n=14 Participants Age matched controls without BPD	Total n=37 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants	7 Participants n=7 Participants	24 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Age, Continuous	62.0 years STANDARD_DEVIATION 5.9 • n=5 Participants	67.5 years STANDARD_DEVIATION 8.8 • n=7 Participants	64.6 years STANDARD_DEVIATION 7.4 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	7 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants	14 participants n=7 Participants	37 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline

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

Outcome measures

Measure	BPD Subjects n=22 Participants Open Label Study Lamotrigine : Lamotrigine with dosage range from 25 mg to 200 mg per day.	Control Subjects n=14 Participants Age matched controls without BPD
Mean Glutamine to Creatine Ratio by Diagnosis at Baseline	.34 mean serum Glutamine to Creatine ratio Standard Deviation .12	.36 mean serum Glutamine to Creatine ratio Standard Deviation .18

PRIMARY outcome

Timeframe: Baseline

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

Outcome measures

Measure	BPD Subjects n=22 Participants Open Label Study Lamotrigine : Lamotrigine with dosage range from 25 mg to 200 mg per day.	Control Subjects n=14 Participants Age matched controls without BPD
Mean Glutamate to Creatine Ratio by Diagnosis at Baseline	.96 mean serum Glutamate to Creatine ratio Standard Deviation .29	.85 mean serum Glutamate to Creatine ratio Standard Deviation .25

PRIMARY outcome

Timeframe: Baseline

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

Outcome measures

Measure	BPD Subjects n=22 Participants Open Label Study Lamotrigine : Lamotrigine with dosage range from 25 mg to 200 mg per day.	Control Subjects n=14 Participants Age matched controls without BPD
Mean N-Acetyl Aspartate (NAA) to Creatine Ratio by Diagnosis at Baseline	0.97 Mean NAA to creatine ratio Standard Deviation 0.14	0.84 Mean NAA to creatine ratio Standard Deviation 0.22

PRIMARY outcome

Timeframe: Baseline

Population: 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.

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.

Outcome measures

Measure	BPD Subjects n=21 Participants Open Label Study Lamotrigine : Lamotrigine with dosage range from 25 mg to 200 mg per day.	Control Subjects Age matched controls without BPD
Associations Between Depression Symptom Severity and Glutamate to Creatine Ratio at Baseline	0.18 Glu:Cr/+10 MADRS Interval -0.02 to 0.38	—

PRIMARY outcome

Timeframe: 8 Weeks

Follow-up Least Squares Mean - Baseline Least Squares Mean

Outcome measures

Measure	BPD Subjects n=13 Participants Open Label Study Lamotrigine : Lamotrigine with dosage range from 25 mg to 200 mg per day.	Control Subjects n=11 Participants Age matched controls without BPD
Estimated Change in Least Squares Mean in Glutamate to Creatine Ratio Between Baseline and Follow-up	0.00 serum Glutamate to Creatine ratio Interval -0.17 to 0.16	-0.12 serum Glutamate to Creatine ratio Interval -0.3 to 0.07

PRIMARY outcome

Timeframe: 8 weeks

Follow-up Least Squares Mean - Baseline Least Squares Mean

Outcome measures

Measure	BPD Subjects n=13 Participants Open Label Study Lamotrigine : Lamotrigine with dosage range from 25 mg to 200 mg per day.	Control Subjects n=11 Participants Age matched controls without BPD
Estimated Change in Least Squares Mean in the Glutamine to Creatine Ratio Between Baseline and Follow-up	0.02 serum Glutamine to Creatine ratio Interval -0.09 to 0.14	0.08 serum Glutamine to Creatine ratio Interval -0.05 to 0.21

PRIMARY outcome

Timeframe: 8 weeks

Follow-up Least Squares Mean - Baseline Least Squares Mean

Outcome measures

Measure	BPD Subjects n=13 Participants Open Label Study Lamotrigine : Lamotrigine with dosage range from 25 mg to 200 mg per day.	Control Subjects n=11 Participants Age matched controls without BPD
Estimated Change in Least Squares Mean in the NAA to Creatine Ratio Between Baseline and Follow-up	0.06 NAA to creatine ratio Interval -0.06 to 0.19	-0.03 NAA to creatine ratio Interval -0.16 to 0.1

PRIMARY outcome

Timeframe: 8 Weeks

Population: 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.

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.

Outcome measures

Measure	BPD Subjects n=11 Participants Open Label Study Lamotrigine : Lamotrigine with dosage range from 25 mg to 200 mg per day.	Control Subjects Age matched controls without BPD
Association of MADRS Changes With Glutamate to Creatine Ratio Changes From Baseline to Follow-up	-.007 Glu:Cr/-10 MADRS Interval -0.24 to 0.23	—

PRIMARY outcome

Timeframe: 8 weeks

Population: 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.

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.

Outcome measures

Measure	BPD Subjects n=11 Participants Open Label Study Lamotrigine : Lamotrigine with dosage range from 25 mg to 200 mg per day.	Control Subjects Age matched controls without BPD
Associations of MADRS Changes With Glutamine to Creatine Ratio Changes From Baseline to Follow-up	0.04 Gln:Cr/-10 MADRS Score Interval -0.07 to 0.14	—

PRIMARY outcome

Timeframe: 8 weeks

Population: 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.

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.

Outcome measures

Measure	BPD Subjects n=11 Participants Open Label Study Lamotrigine : Lamotrigine with dosage range from 25 mg to 200 mg per day.	Control Subjects Age matched controls without BPD
Associations of MADRS Changes With NAA to Creatine Ratio Changes From Baseline to Follow-up	0.05 NAA:Cr/-10 MADRS Interval -0.04 to 0.15	—

PRIMARY outcome

Timeframe: Baseline

Population: MADRS scores were available for 27 eligible bipolar subjects and 14 eligible controls.

The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed.

Outcome measures

Measure	BPD Subjects n=27 Participants Open Label Study Lamotrigine : Lamotrigine with dosage range from 25 mg to 200 mg per day.	Control Subjects n=14 Participants Age matched controls without BPD
Mean Montgomery Asberg Depression Rating Scale (MADRS) Score at Baseline	24.78 units on a scale Standard Deviation 6.65	1.03 units on a scale Standard Deviation 1.55

PRIMARY outcome

Timeframe: 8 Weeks

Population: MADRS scores were available for 16 bipolar subjects who completed the protocol and 8 healthy controls.

The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed.

Outcome measures

Measure	BPD Subjects n=16 Participants Open Label Study Lamotrigine : Lamotrigine with dosage range from 25 mg to 200 mg per day.	Control Subjects n=8 Participants Age matched controls without BPD
Means of MADRS Scores at 8 Weeks	18.31 units on a scale Standard Deviation 9.41	1.38 units on a scale Standard Deviation 1.51

Adverse Events

Control Subjects

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

BPD Subjects

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure	Control Subjects n=24 participants at risk Age matched controls without BPD	BPD Subjects n=45 participants at risk
Injury, poisoning and procedural complications Loss of consciousness	0.00% 0/24	2.2% 1/45 • Number of events 1
Psychiatric disorders Mania	0.00% 0/24	2.2% 1/45 • Number of events 1

Other adverse events

Measure	Control Subjects n=24 participants at risk Age matched controls without BPD	BPD Subjects n=45 participants at risk
Skin and subcutaneous tissue disorders Rash	0.00% 0/24	2.2% 1/45 • Number of events 1
Skin and subcutaneous tissue disorders Blister	0.00% 0/24	2.2% 1/45 • Number of events 1
Psychiatric disorders mania	0.00% 0/24	2.2% 1/45 • Number of events 1
Eye disorders Blurry Vision	0.00% 0/24	2.2% 1/45 • Number of events 1
Psychiatric disorders Insomnia	0.00% 0/24	8.9% 4/45 • Number of events 4
General disorders Decreased balance	0.00% 0/24	6.7% 3/45 • Number of events 3
Gastrointestinal disorders Stomach upset	0.00% 0/24	4.4% 2/45 • Number of events 2
Psychiatric disorders Irritability	0.00% 0/24	2.2% 1/45 • Number of events 1
General disorders Headache	0.00% 0/24	4.4% 2/45 • Number of events 2
Respiratory, thoracic and mediastinal disorders Runny Nose	0.00% 0/24	2.2% 1/45 • Number of events 1
Metabolism and nutrition disorders Weight gain	0.00% 0/24	2.2% 1/45 • Number of events 1

Additional Information

Dr. Brent Forester

McLean Hospital

Phone: (617) 855-3622

Email: bforester@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place