Trial Outcomes & Findings for Bipolar Depression Before and After Lamotrigine Treatment (NCT NCT01042496)
NCT ID: NCT01042496
Last Updated: 2016-02-08
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
72 participants
Primary outcome timeframe
baseline, 12 weeks
Results posted on
2016-02-08
Participant Flow
Subjects were recruited from the Mayo Clinic in Rochester, Minnesota.
39 subjects signed informed consent for the Bipolar Group, but 9 were screen failures, and one subject signed consent but did not start the study. 33 subjects signed informed consent for the Healthy Control group, and all of these subjects completed the study.
Participant milestones
| Measure |
Bipolar Group
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.
Lamotrigine: 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.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
Control Group
Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
|---|---|---|
|
Overall Study
STARTED
|
29
|
33
|
|
Overall Study
COMPLETED
|
29
|
33
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bipolar Depression Before and After Lamotrigine Treatment
Baseline characteristics by cohort
| Measure |
Bipolar Group
n=29 Participants
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.
Lamotrigine: 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.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
Control Group
n=33 Participants
Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
Total
n=62 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
36.10 years
STANDARD_DEVIATION 13.44 • n=5 Participants
|
35.18 years
STANDARD_DEVIATION 10.1 • n=7 Participants
|
35.61 years
STANDARD_DEVIATION 11.69 • n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
29 participants
n=5 Participants
|
33 participants
n=7 Participants
|
62 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: baseline, 12 weeksPopulation: The control group only did the MADRS depression rating scale at baseline. 25 participants in the Bipolar group took the MADRS depression rating scale at 12 weeks.
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.
Outcome measures
| Measure |
Bipolar Group
n=29 Participants
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.
Lamotrigine: 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.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
Control Group
n=33 Participants
Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
Bipolar Lamotrigine Non-Responders Group
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.
Lamotrigine: 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.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
Non-responders were those bipolar participants who did not achieve remission (defined as a Montgomery Asberg Depression Rating Scale (MADRS) score \<12 at week 12).
|
Bipolar Lamotrigine Group as Whole
Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (DLPFC) before and after treatment with Lamotrigine.
Lamotrigine: 12 week open trial: 25mg/day for 2 weeks, 50mg/day for 2 weeks, 100mg/day for 2 weeks, 200mg/day for 6 weeks.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (DLPFC).
|
|---|---|---|---|---|
|
Mean Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group
Baseline
|
27.79 units on a scale
Standard Deviation 5.80
|
0.30 units on a scale
Standard Deviation 0.64
|
—
|
—
|
|
Mean Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group
12 weeks
|
14.28 units on a scale
Standard Deviation 11.67
|
NA units on a scale
Standard Deviation NA
The control group only did the MADRS depression rating scale at baseline.
|
—
|
—
|
SECONDARY outcome
Timeframe: baseline, after 12 weeksPopulation: Sample sizes varied due to imaging results/scan viability. Excessive noise resulted in poor metabolite readings which in-turn were not used in the final analysis. Baseline: control group MACC n=7, LDLPC n=8, Bipolar group MACC n=18, LDLPC n=27. Bipolar group 12 weeks MACC n=12, LDLPC n=16. The control group did not do the procedure at 12 weeks.
Two different MRS sequences were used to measure the brain chemicals in in anterior cingulate and left dorsal lateral prefrontal cortex : an intermediate echo-time PRESS sequence and a 2D J-resolved averaged PRESS sequence. (Note: The intermediate echo-time PRESS sequence was used for this outcome measure.) Spectroscopic data were inspected for quality; subjects whose data were contaminated by artifact were excluded from the study. Spectra were then processed using LCModel to quantify brain chemical levels. Regular brain MRI images were segmented, yielding a map of the amount of cerebrospinal fluid (CSF); the MRS voxel was overlaid onto the CSF map and the fraction of CSF was measured. This CSF corrected measurement was used for statistical analysis.
Outcome measures
| Measure |
Bipolar Group
n=28 Participants
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.
Lamotrigine: 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.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
Control Group
n=8 Participants
Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
Bipolar Lamotrigine Non-Responders Group
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.
Lamotrigine: 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.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
Non-responders were those bipolar participants who did not achieve remission (defined as a Montgomery Asberg Depression Rating Scale (MADRS) score \<12 at week 12).
|
Bipolar Lamotrigine Group as Whole
Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (DLPFC) before and after treatment with Lamotrigine.
Lamotrigine: 12 week open trial: 25mg/day for 2 weeks, 50mg/day for 2 weeks, 100mg/day for 2 weeks, 200mg/day for 6 weeks.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (DLPFC).
|
|---|---|---|---|---|
|
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 GLX measured in MACC
|
15.08 Institutional Units (IU)
Standard Deviation 3.88
|
11.98 Institutional Units (IU)
Standard Deviation 2.06
|
—
|
—
|
|
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
12 Weeks GLX measured in MACC
|
12.69 Institutional Units (IU)
Standard Deviation 4.05
|
NA Institutional Units (IU)
Standard Deviation NA
The control group did not do the procedure at 12 weeks.
|
—
|
—
|
|
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 GLX measured in LDLPC
|
14.0 Institutional Units (IU)
Standard Deviation 2.7
|
12.9 Institutional Units (IU)
Standard Deviation 1.4
|
—
|
—
|
|
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
12 Weeks GLX measured in LDLPC
|
14.1 Institutional Units (IU)
Standard Deviation 2.7
|
NA Institutional Units (IU)
Standard Deviation NA
The control group did not do the procedure at 12 weeks.
|
—
|
—
|
SECONDARY outcome
Timeframe: baseline, 12 weeksPopulation: Samples varied due to imaging results/scan viability. Baseline: control group MACC (M) and LDLPC (L) n=8, BP whole M n=28 (3 didn't complete), L n=27, BP Responders M n=13, L n=11, BP nonresponders M and L n=12; BP whole 12 weeks M and L n=16. BP Responders M and L n=10, BP nonresponders M and L n=6. Controls didn't do the procedure at 12 weeks.
Two different MRS sequences were used to measure the brain chemicals in a single 2 x 2 x 2 cm cube located in the center of anterior cingulate cortex: an intermediate echo-time PRESS sequence and a 2D J-resolved averaged PRESS sequence. (Note: The intermediate echo-time PRESS sequence was used for this outcome measure.) Spectroscopic data were inspected for quality; subjects whose data were contaminated by artifact were excluded from the study. Spectra were then processed using LCModel to quantify brain chemical levels. Regular brain MRI images were segmented, yielding a map of the amount of CSF in the head. The MRS voxel was overlaid onto the CSF map and the fraction of CSF within the voxel measured. This CSF-corrected measurement was used for statistical analysis.
Outcome measures
| Measure |
Bipolar Group
n=13 Participants
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.
Lamotrigine: 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.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
Control Group
n=8 Participants
Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
Bipolar Lamotrigine Non-Responders Group
n=12 Participants
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.
Lamotrigine: 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.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
Non-responders were those bipolar participants who did not achieve remission (defined as a Montgomery Asberg Depression Rating Scale (MADRS) score \<12 at week 12).
|
Bipolar Lamotrigine Group as Whole
n=28 Participants
Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (DLPFC) before and after treatment with Lamotrigine.
Lamotrigine: 12 week open trial: 25mg/day for 2 weeks, 50mg/day for 2 weeks, 100mg/day for 2 weeks, 200mg/day for 6 weeks.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (DLPFC).
|
|---|---|---|---|---|
|
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
LDLPC Baseline NAA
|
19.5 Institutional Units (IU)
Standard Deviation 1.9
|
20.1 Institutional Units (IU)
Standard Deviation 1.5
|
21.0 Institutional Units (IU)
Standard Deviation 2.8
|
20.0 Institutional Units (IU)
Standard Deviation 2.5
|
|
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
LDLPC 12 weeks NAA
|
20.3 Institutional Units (IU)
Standard Deviation 2.1
|
NA Institutional Units (IU)
Standard Deviation NA
The control group did not do the procedure at 12 weeks.
|
20.8 Institutional Units (IU)
Standard Deviation 2.9
|
20.5 Institutional Units (IU)
Standard Deviation 2.4
|
|
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
MACC Baseline NAA
|
15.7 Institutional Units (IU)
Standard Deviation 2.9
|
17.51 Institutional Units (IU)
Standard Deviation 1.77
|
15.2 Institutional Units (IU)
Standard Deviation 3.3
|
15.4 Institutional Units (IU)
Standard Deviation 3.0
|
|
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
MACC 12 weeks NAA
|
14.3 Institutional Units (IU)
Standard Deviation 3.2
|
NA Institutional Units (IU)
Standard Deviation NA
The control group did not do the procedure at 12 weeks.
|
14.9 Institutional Units (IU)
Standard Deviation 3.8
|
14.5 Institutional Units (IU)
Standard Deviation 3.4
|
SECONDARY outcome
Timeframe: baseline, 12 weeksPopulation: Sample sizes varied due to imaging results/scan viability. Excessive noise resulted in poor metabolite readings which in-turn were not used in the final analysis. Baseline: control group MACC n=8, LDLPC n=8, Bipolar group MACC n=13, LDLPC n=13. Bipolar group 12 weeks MACC n=8, LDLPC n=17. The control group did not do the procedure at 12 weeks.
Two different MRS sequences were used to measure the brain chemicals in a single 2 x 2 x 2 cm cube located in the center of anterior cingulate cortex: an intermediate echo-time PRESS sequence and a 2D J-resolved averaged PRESS sequence. (Note: The 2D J-resolved averaged PRESS sequence was used for this outcome measure.) Spectroscopic data were inspected for quality; subjects whose data were contaminated by artifact were excluded from the study. Spectra were then processed using LCModel to quantify brain chemical levels. Regular brain MRI images were segmented, yielding a map of the amount of CSF in the head. The MRS voxel was overlaid onto the CSF map and the fraction of CSF within the voxel measured. This CSF-corrected measurement was then used for statistical analysis.
Outcome measures
| Measure |
Bipolar Group
n=17 Participants
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.
Lamotrigine: 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.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
Control Group
n=8 Participants
Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
Bipolar Lamotrigine Non-Responders Group
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.
Lamotrigine: 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.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
Non-responders were those bipolar participants who did not achieve remission (defined as a Montgomery Asberg Depression Rating Scale (MADRS) score \<12 at week 12).
|
Bipolar Lamotrigine Group as Whole
Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (DLPFC) before and after treatment with Lamotrigine.
Lamotrigine: 12 week open trial: 25mg/day for 2 weeks, 50mg/day for 2 weeks, 100mg/day for 2 weeks, 200mg/day for 6 weeks.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (DLPFC).
|
|---|---|---|---|---|
|
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 MACC
|
147.55 Institutional Units (IU)
Standard Deviation 32.57
|
157.51 Institutional Units (IU)
Standard Deviation 36.17
|
—
|
—
|
|
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
12 Weeks MACC
|
134 Institutional Units (IU)
Standard Deviation 13.5
|
NA Institutional Units (IU)
Standard Deviation NA
The control group did not do the procedure at 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 LDLPC
|
65.4 Institutional Units (IU)
Standard Deviation 15.5
|
64.1 Institutional Units (IU)
Standard Deviation 12.6
|
—
|
—
|
|
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
12 Weeks LDLPC
|
63.5 Institutional Units (IU)
Standard Deviation 11.6
|
NA Institutional Units (IU)
Standard Deviation NA
The control group did not do the procedure at 12 weeks.
|
—
|
—
|
SECONDARY outcome
Timeframe: baselinePopulation: Sample sizes varied between both scanning locations LDLPC and MACC and between metabolites due to imaging results/scan viability. Some subject scans yielded more viable information/ less noise during the scan process. Excessive noise resulted in poor metabolite readings which in-turn were not used in the final analysis.
Two different MRS sequences were used to measure the brain chemicals in a single 2 x 2 x 2 cm cube located in the center of anterior cingulate cortex: an intermediate echo-time PRESS sequence and a 2D J-resolved averaged PRESS sequence. (Note: The 2D J-resolved averaged PRESS sequence was used for this outcome measure.) Spectroscopic data were inspected for quality; subjects whose data were contaminated by artifact were excluded from the study. Spectra were then processed using LCModel to quantify brain chemical levels. Regular brain MRI images were segmented, yielding a map of the amount of CSF in the head. The MRS voxel was overlaid onto the CSF map and the fraction of CSF within the voxel measured. This CSF-corrected measurement was then used for statistical analysis.
Outcome measures
| Measure |
Bipolar Group
n=6 Participants
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.
Lamotrigine: 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.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
Control Group
Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
Bipolar Lamotrigine Non-Responders Group
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.
Lamotrigine: 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.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
Non-responders were those bipolar participants who did not achieve remission (defined as a Montgomery Asberg Depression Rating Scale (MADRS) score \<12 at week 12).
|
Bipolar Lamotrigine Group as Whole
Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (DLPFC) before and after treatment with Lamotrigine.
Lamotrigine: 12 week open trial: 25mg/day for 2 weeks, 50mg/day for 2 weeks, 100mg/day for 2 weeks, 200mg/day for 6 weeks.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (DLPFC).
|
|---|---|---|---|---|
|
Glutamine/Glutamate Ratio Measured in the LDLPC at Baseline Using the ProFit Magnetic Resonance Spectroscopy (MRS) Technique
|
1.27 ratio
Standard Deviation .62
|
—
|
—
|
—
|
Adverse Events
Bipolar Group
Serious events: 5 serious events
Other events: 6 other events
Deaths: 0 deaths
Control Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bipolar Group
n=29 participants at risk
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.
Lamotrigine: 12 week open trial: 25mg/day for 2 weeks, 50mg/day for 2 weeks, 100mg/day for 2 weeks, 200mg/day for 6 weeks
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
Control Group
n=33 participants at risk
Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
|---|---|---|
|
Psychiatric disorders
Hospitalization due to progression of disease
|
3.4%
1/29 • Number of events 1
|
0.00%
0/33
|
|
Psychiatric disorders
Admitted to ER due to symptoms
|
3.4%
1/29 • Number of events 1
|
0.00%
0/33
|
|
Psychiatric disorders
Death
|
3.4%
1/29 • Number of events 1
|
0.00%
0/33
|
|
Psychiatric disorders
Worsening of bipolar symptoms
|
3.4%
1/29 • Number of events 1
|
0.00%
0/33
|
|
Psychiatric disorders
Withdrawal from study due to decrease in mood
|
3.4%
1/29 • Number of events 1
|
0.00%
0/33
|
Other adverse events
| Measure |
Bipolar Group
n=29 participants at risk
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.
Lamotrigine: 12 week open trial: 25mg/day for 2 weeks, 50mg/day for 2 weeks, 100mg/day for 2 weeks, 200mg/day for 6 weeks
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
Control Group
n=33 participants at risk
Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Bruise on back of head near ossiput
|
3.4%
1/29 • Number of events 1
|
0.00%
0/33
|
|
Blood and lymphatic system disorders
Swollen lymph node
|
3.4%
1/29 • Number of events 1
|
0.00%
0/33
|
|
Skin and subcutaneous tissue disorders
Rash on left knee
|
3.4%
1/29 • Number of events 1
|
0.00%
0/33
|
|
Hepatobiliary disorders
Abnormal high AST level at study exit
|
3.4%
1/29 • Number of events 1
|
0.00%
0/33
|
|
Blood and lymphatic system disorders
Abnormal high GGT level at study exit
|
3.4%
1/29 • Number of events 1
|
0.00%
0/33
|
|
Musculoskeletal and connective tissue disorders
Paresthesia of Right Shoulder Blade
|
3.4%
1/29 • Number of events 1
|
0.00%
0/33
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
3.4%
1/29 • Number of events 1
|
0.00%
0/33
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place