Trial Outcomes & Findings for 12-Week Study Evaluating the Efficacy, Safety, and Tolerability of Adjunctive Infliximab for Bipolar I/II Depression (NCT NCT02363738)
NCT ID: NCT02363738
Last Updated: 2021-07-28
Results Overview
Baseline and Week 12 Montgomery-Asberg Depression Rating Scale scores are provided, with the range of possible values on the scale from 0 to 60. The higher the score, the worse the overall depressive symptoms.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
60 participants
Primary outcome timeframe
Up to 12 weeks
Results posted on
2021-07-28
Participant Flow
Participant milestones
| Measure |
Infliximab
Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation
Infliximab: Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation. Infliximab will be prescribed adjunctively to a conventional mood stabilizer or atypical antipsychotic agent.
|
Saline (Placebo)
Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency.
Saline: Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency and will be administered adjunctively to conventional mood stabilizer or atypical antipsychotic agent.
|
|---|---|---|
|
Overall Study
STARTED
|
29
|
31
|
|
Overall Study
COMPLETED
|
21
|
26
|
|
Overall Study
NOT COMPLETED
|
8
|
5
|
Reasons for withdrawal
| Measure |
Infliximab
Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation
Infliximab: Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation. Infliximab will be prescribed adjunctively to a conventional mood stabilizer or atypical antipsychotic agent.
|
Saline (Placebo)
Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency.
Saline: Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency and will be administered adjunctively to conventional mood stabilizer or atypical antipsychotic agent.
|
|---|---|---|
|
Overall Study
Adverse Event
|
5
|
2
|
|
Overall Study
Lack of Efficacy
|
1
|
2
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
Baseline Characteristics
12-Week Study Evaluating the Efficacy, Safety, and Tolerability of Adjunctive Infliximab for Bipolar I/II Depression
Baseline characteristics by cohort
| Measure |
Infliximab
n=28 Participants
Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation
Infliximab: Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation. Infliximab will be prescribed adjunctively to a conventional mood stabilizer or atypical antipsychotic agent.
|
Saline (Placebo)
n=30 Participants
Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency.
Saline: Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency and will be administered adjunctively to conventional mood stabilizer or atypical antipsychotic agent.
|
Total
n=58 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
45 years
STANDARD_DEVIATION 11.7 • n=5 Participants
|
46.8 years
STANDARD_DEVIATION 10.2 • n=7 Participants
|
45.71 years
STANDARD_DEVIATION 10.91 • n=5 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
24 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
26 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
BMI
|
34.5 kg/m^2
STANDARD_DEVIATION 10 • n=5 Participants
|
34.6 kg/m^2
STANDARD_DEVIATION 8 • n=7 Participants
|
34.5 kg/m^2
STANDARD_DEVIATION 8.95 • n=5 Participants
|
|
Number of lifetime psychiatric hospitalizations
|
1.8 Hospitalizations
STANDARD_DEVIATION 1.9 • n=5 Participants
|
1.6 Hospitalizations
STANDARD_DEVIATION 2.0 • n=7 Participants
|
1.65 Hospitalizations
STANDARD_DEVIATION 2.0 • n=5 Participants
|
|
Baseline MADRS total score
|
30.6 units on a scale
STANDARD_DEVIATION 7.2 • n=5 Participants
|
29.5 units on a scale
STANDARD_DEVIATION 7 • n=7 Participants
|
30 units on a scale
STANDARD_DEVIATION 7.01 • n=5 Participants
|
|
Baseline YMRS total score
|
3.5 units on a scale
STANDARD_DEVIATION 3.0 • n=5 Participants
|
4.4 units on a scale
STANDARD_DEVIATION 4.2 • n=7 Participants
|
3.9 units on a scale
STANDARD_DEVIATION 3.5 • n=5 Participants
|
|
Bipolar I disorder
|
16 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Bipolar II disorder
|
12 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Educational level
High school
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Educational level
College or university
|
17 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Educational level
Graduate school
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
CRP level, age-adjusted
|
4.5 mg/L
STANDARD_DEVIATION 3.3 • n=5 Participants
|
7.3 mg/L
STANDARD_DEVIATION 8.1 • n=7 Participants
|
7.0 mg/L
STANDARD_DEVIATION 8.3 • n=5 Participants
|
|
Inflammatory criteria met
CRP level greater than or equal to 5 mg/L
|
10 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Inflammatory criteria met
Obesity combined with hypertension or dyslipidemia
|
20 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
|
Inflammatory criteria met
Diabetes type 1 or 2
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Inflammatory criteria met
Inflammatory bowel disorder
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Inflammatory criteria met
Rheumatologic disorder
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Inflammatory criteria met
Daily cigarette smoking
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Inflammatory criteria met
Migraine headaches
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Medications
Lithium carbonate
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Medications
Valproate sodium
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Medications
Quetiapine fumarate
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Medications
Olanzapine and fluoxetine hydrochloride
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Medications
Lurasidone hydrochloride
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Medications
Lamotrigine
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Medications
Antidepressant
|
13 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 12 weeksPopulation: The modified intent-to-treat analysis included all participants who had received at least 1 infusion of study medication and completed at least 1 after-baseline efficacy assessment. One participant from the Infliximab arm and one participant from the placebo arm were excluded fromt he analyses because they did not complete at least one efficacy assessment after baseline.
Baseline and Week 12 Montgomery-Asberg Depression Rating Scale scores are provided, with the range of possible values on the scale from 0 to 60. The higher the score, the worse the overall depressive symptoms.
Outcome measures
| Measure |
Infliximab
n=28 Participants
Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation
Infliximab: Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation. Infliximab will be prescribed adjunctively to a conventional mood stabilizer or atypical antipsychotic agent.
|
Saline (Placebo)
n=30 Participants
Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency.
Saline: Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency and will be administered adjunctively to conventional mood stabilizer or atypical antipsychotic agent.
|
|---|---|---|
|
Baseline and Week 12 Montgomery-Asberg Depression Rating Scale (MADRS) Scores
Baseline
|
29.61 units on a scale
Standard Error 1.36
|
27.79 units on a scale
Standard Error 1.59
|
|
Baseline and Week 12 Montgomery-Asberg Depression Rating Scale (MADRS) Scores
Week. 12
|
18.64 units on a scale
Standard Error 2.40
|
16.06 units on a scale
Standard Error 2.00
|
PRIMARY outcome
Timeframe: Up to 6 weeksPopulation: The modified intent-to-treat analysis included all participants who had received at least 1 infusion of study medication and completed at least 1 after-baseline efficacy assessment. One participant from the Infliximab arm and one participant from the placebo arm were excluded fromt he analyses because they did not complete at least one efficacy assessment after baseline.
Baseline and Week 6 Montgomery-Asberg Depression Rating Scale (MADRS) scores, where the range of possible values on the scale is from 0 to 60. The higher the score, the worse the overall depressive symptoms.
Outcome measures
| Measure |
Infliximab
n=28 Participants
Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation
Infliximab: Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation. Infliximab will be prescribed adjunctively to a conventional mood stabilizer or atypical antipsychotic agent.
|
Saline (Placebo)
n=30 Participants
Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency.
Saline: Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency and will be administered adjunctively to conventional mood stabilizer or atypical antipsychotic agent.
|
|---|---|---|
|
Baseline and Week 6 Montgomery-Asberg Depression Rating Scale (MADRS) Scores
Baseline
|
29.61 units on a scale
Standard Error 1.36
|
27.79 units on a scale
Standard Error 1.59
|
|
Baseline and Week 6 Montgomery-Asberg Depression Rating Scale (MADRS) Scores
Week 6
|
19.44 units on a scale
Standard Error 2.27
|
20.94 units on a scale
Standard Error 2.29
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: The number of total participants analyzed is lower than those previously reported in the primary outcome measure as only a subgroup of participants underwent this additional and optional MRS testing.
Changes in prefrontal metabolites concentration of N-acetylaspartate, using proton-magnetic resonance spectroscopy (1H-MRS), adjusted for age, sex, baseline values and % gray matter in the spectroscopic region of interest.
Outcome measures
| Measure |
Infliximab
n=15 Participants
Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation
Infliximab: Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation. Infliximab will be prescribed adjunctively to a conventional mood stabilizer or atypical antipsychotic agent.
|
Saline (Placebo)
n=18 Participants
Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency.
Saline: Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency and will be administered adjunctively to conventional mood stabilizer or atypical antipsychotic agent.
|
|---|---|---|
|
Changes in Brain N-acetylaspartate Levels
Baseline
|
5.67 mmol/kg
Standard Error 0.09
|
5.65 mmol/kg
Standard Error 0.09
|
|
Changes in Brain N-acetylaspartate Levels
Week 12
|
5.71 mmol/kg
Standard Error 0.21
|
5.81 mmol/kg
Standard Error 0.18
|
SECONDARY outcome
Timeframe: Baseline to 12 weeksPopulation: Three participants in the Infliximab group did not complete at least one post-baseline efficacy assessment. Three participants did not complete at least one post-baseline efficacy assessment.
Change in the Snaith-Hamilton Pleasure Scale (SHAPS) total score. Total score range of 14 to 56, with greater scores indicative of greater hedonic capacity.
Outcome measures
| Measure |
Infliximab
n=25 Participants
Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation
Infliximab: Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation. Infliximab will be prescribed adjunctively to a conventional mood stabilizer or atypical antipsychotic agent.
|
Saline (Placebo)
n=27 Participants
Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency.
Saline: Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency and will be administered adjunctively to conventional mood stabilizer or atypical antipsychotic agent.
|
|---|---|---|
|
Changes in Anhedonia
Baseline
|
34.04 Score on a scale
Standard Error 1.73
|
34.8 Score on a scale
Standard Error 1.45
|
|
Changes in Anhedonia
Week 12
|
37.17 Score on a scale
Standard Error 1.5
|
40.79 Score on a scale
Standard Error 1.69
|
Adverse Events
Infliximab
Serious events: 1 serious events
Other events: 4 other events
Deaths: 1 deaths
Saline (Placebo)
Serious events: 2 serious events
Other events: 0 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Infliximab
n=29 participants at risk
Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation
Infliximab: Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation. Infliximab will be prescribed adjunctively to a conventional mood stabilizer or atypical antipsychotic agent.
|
Saline (Placebo)
n=31 participants at risk
Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency.
Saline: Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency and will be administered adjunctively to conventional mood stabilizer or atypical antipsychotic agent.
|
|---|---|---|
|
Nervous system disorders
Mortality
|
3.4%
1/29 • Number of events 1 • Adverse event data were collected from screening (prior to baseline) through the completion of the study at week 12 (minimum of 3 months).
|
0.00%
0/31 • Adverse event data were collected from screening (prior to baseline) through the completion of the study at week 12 (minimum of 3 months).
|
|
Social circumstances
Mortality
|
0.00%
0/29 • Adverse event data were collected from screening (prior to baseline) through the completion of the study at week 12 (minimum of 3 months).
|
3.2%
1/31 • Number of events 1 • Adverse event data were collected from screening (prior to baseline) through the completion of the study at week 12 (minimum of 3 months).
|
|
Psychiatric disorders
Hospitalization
|
0.00%
0/29 • Adverse event data were collected from screening (prior to baseline) through the completion of the study at week 12 (minimum of 3 months).
|
3.2%
1/31 • Number of events 1 • Adverse event data were collected from screening (prior to baseline) through the completion of the study at week 12 (minimum of 3 months).
|
Other adverse events
| Measure |
Infliximab
n=29 participants at risk
Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation
Infliximab: Intravenous infliximab (5mg/kg) at baseline, week 2 and 6 under clinical observation. Infliximab will be prescribed adjunctively to a conventional mood stabilizer or atypical antipsychotic agent.
|
Saline (Placebo)
n=31 participants at risk
Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency.
Saline: Intravenous placebo (saline solution) at baseline, week 2 and 6 under clinical observation. Placebo will be matched to infliximab in color and consistency and will be administered adjunctively to conventional mood stabilizer or atypical antipsychotic agent.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Skin Rash
|
3.4%
1/29 • Number of events 1 • Adverse event data were collected from screening (prior to baseline) through the completion of the study at week 12 (minimum of 3 months).
|
0.00%
0/31 • Adverse event data were collected from screening (prior to baseline) through the completion of the study at week 12 (minimum of 3 months).
|
|
Skin and subcutaneous tissue disorders
Hair loss
|
3.4%
1/29 • Number of events 1 • Adverse event data were collected from screening (prior to baseline) through the completion of the study at week 12 (minimum of 3 months).
|
0.00%
0/31 • Adverse event data were collected from screening (prior to baseline) through the completion of the study at week 12 (minimum of 3 months).
|
|
Musculoskeletal and connective tissue disorders
Reactive arthritis
|
3.4%
1/29 • Number of events 1 • Adverse event data were collected from screening (prior to baseline) through the completion of the study at week 12 (minimum of 3 months).
|
0.00%
0/31 • Adverse event data were collected from screening (prior to baseline) through the completion of the study at week 12 (minimum of 3 months).
|
|
Hepatobiliary disorders
Abnormal liver function enzymes
|
3.4%
1/29 • Number of events 1 • Adverse event data were collected from screening (prior to baseline) through the completion of the study at week 12 (minimum of 3 months).
|
0.00%
0/31 • Adverse event data were collected from screening (prior to baseline) through the completion of the study at week 12 (minimum of 3 months).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place