Trial Outcomes & Findings for A Study of Infliximab for Treatment Resistant Major Depression (NCT NCT00463580)
NCT ID: NCT00463580
Last Updated: 2025-07-08
Results Overview
The HDRS is a 17-item survey asking respondents to rate the degree of depressive symptoms they are feeling on a scale of 0 to 2-4, where 0 means the symptom is absent and 2-4 means the symptom is very strong. Total scores can range from 0 to 52 where higher scores represent greater symptom severity. Scores of 0-7 are considered normal, scores of 8-16 indicates mild depression, scores of 17-23 indicate moderate depression, and scores of 24 and greater indicate severe depression.
COMPLETED
PHASE4
60 participants
Baseline, Weeks 1, 2, 4, 6, 8, 10 and 12
2025-07-08
Participant Flow
Participants were enrolled at Emory University in Atlanta, Georgia. Enrollment began in December 2008 and all participation ended in June 2011.
Group assignment was stratified based on sex and screening values of C-reactive protein (CRP) concentration (less than 2mg/L or 2mg/L and greater).
Participant milestones
| Measure |
Infliximab
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
|
Placebo
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
|
|---|---|---|
|
Overall Study
STARTED
|
30
|
30
|
|
Overall Study
COMPLETED
|
27
|
28
|
|
Overall Study
NOT COMPLETED
|
3
|
2
|
Reasons for withdrawal
| Measure |
Infliximab
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
|
Placebo
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Schedule conflict
|
2
|
0
|
|
Overall Study
Medical/psychiatric complications
|
0
|
2
|
Baseline Characteristics
A Study of Infliximab for Treatment Resistant Major Depression
Baseline characteristics by cohort
| Measure |
Infliximab
n=30 Participants
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
|
Placebo
n=30 Participants
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
42.5 years
STANDARD_DEVIATION 8.2 • n=5 Participants
|
44.3 years
STANDARD_DEVIATION 9.4 • n=7 Participants
|
43.4 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
23 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
Hamilton Depression Rating Scale-17 item (HDRS-17)
|
24.1 scores on a scale
STANDARD_DEVIATION 4.0 • n=5 Participants
|
23.6 scores on a scale
STANDARD_DEVIATION 3.8 • n=7 Participants
|
23.8 scores on a scale
STANDARD_DEVIATION 3.9 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Weeks 1, 2, 4, 6, 8, 10 and 12Population: All participants beginning the study are included in this analysis.
The HDRS is a 17-item survey asking respondents to rate the degree of depressive symptoms they are feeling on a scale of 0 to 2-4, where 0 means the symptom is absent and 2-4 means the symptom is very strong. Total scores can range from 0 to 52 where higher scores represent greater symptom severity. Scores of 0-7 are considered normal, scores of 8-16 indicates mild depression, scores of 17-23 indicate moderate depression, and scores of 24 and greater indicate severe depression.
Outcome measures
| Measure |
Infliximab
n=30 Participants
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
|
Placebo
n=30 Participants
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
|
Baseline Hs-CRP of > 3
Participants with a baseline hs-CRP value greater than 3 mg/L.
|
Baseline Hs-CRP of >5 mg/L
Participants with a baseline hs-CRP value greater than 5 mg/L.
|
|---|---|---|---|---|
|
Hamilton Depression Rating Scale 17 (HDRS-17) Scores
Baseline
|
24.1 scores on a scale
Standard Deviation 4.0
|
23.6 scores on a scale
Standard Deviation 3.8
|
—
|
—
|
|
Hamilton Depression Rating Scale 17 (HDRS-17) Scores
Week 1
|
20.8 scores on a scale
Standard Deviation 6.7
|
20.4 scores on a scale
Standard Deviation 4.9
|
—
|
—
|
|
Hamilton Depression Rating Scale 17 (HDRS-17) Scores
Week 2
|
18.8 scores on a scale
Standard Deviation 7.0
|
18.3 scores on a scale
Standard Deviation 6.2
|
—
|
—
|
|
Hamilton Depression Rating Scale 17 (HDRS-17) Scores
Week 4
|
18.8 scores on a scale
Standard Deviation 6.7
|
16.3 scores on a scale
Standard Deviation 5.7
|
—
|
—
|
|
Hamilton Depression Rating Scale 17 (HDRS-17) Scores
Week 6
|
17.9 scores on a scale
Standard Deviation 6.2
|
16.4 scores on a scale
Standard Deviation 5.9
|
—
|
—
|
|
Hamilton Depression Rating Scale 17 (HDRS-17) Scores
Week 8
|
17.5 scores on a scale
Standard Deviation 7.4
|
14.8 scores on a scale
Standard Deviation 6.8
|
—
|
—
|
|
Hamilton Depression Rating Scale 17 (HDRS-17) Scores
Week 10
|
17.4 scores on a scale
Standard Deviation 8.4
|
13.6 scores on a scale
Standard Deviation 8.3
|
—
|
—
|
|
Hamilton Depression Rating Scale 17 (HDRS-17) Scores
Week 12
|
16.6 scores on a scale
Standard Deviation 8.4
|
14.0 scores on a scale
Standard Deviation 8.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 12Population: All participants beginning the study are included in this analysis.
The number of participants with a 50% reduction in Hamilton Depression Rating Scale (HDRS) scores at any study point are presented here. The HDRS is a 17-item survey asking respondents to rate the degree of depressive symptoms they are feeling on a scale of 0 to 2-4, where 0 means the symptom is absent and 2-4 means the symptom is very strong. Total scores can range from 0 to 52 where higher scores represent greater symptom severity. Scores of 0-7 are considered normal, scores of 8-16 indicates mild depression, scores of 17-23 indicate moderate depression, and scores of 24 and greater indicate severe depression.
Outcome measures
| Measure |
Infliximab
n=30 Participants
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
|
Placebo
n=30 Participants
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
|
Baseline Hs-CRP of > 3
Participants with a baseline hs-CRP value greater than 3 mg/L.
|
Baseline Hs-CRP of >5 mg/L
Participants with a baseline hs-CRP value greater than 5 mg/L.
|
|---|---|---|---|---|
|
Number of Participants With a 50% Reduction in Hamilton Depression Rating Scale (HDRS) Scores
|
15 participants
|
15 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 12Population: All participants beginning the study are included in this analysis.
The number of participants achieving depression remission are presented here. Depression remission is defined as an HDRS score of ≤7 or a Clinical Global Impression-Improvement (CGI-I) score of 1. The HDRS is a 17-item survey asking respondents to rate the degree of depressive symptoms they are feeling on a scale of 0 to 2-4, where 0 means the symptom is absent and 2-4 means the symptom is very strong. Total scores can range from 0 to 52 where higher scores represent greater symptom severity. Scores of 0-7 are considered normal, scores of 8-16 indicates mild depression, scores of 17-23 indicate moderate depression, and scores of 24 and greater indicate severe depression. The CGI-I scale includes a single item where a health care provider rates the participant's level of clinical improvement on a scale of 1 to 7 where 1 = very much improved since initiation of treatment and 7 = very much worse since initiation of treatment.
Outcome measures
| Measure |
Infliximab
n=30 Participants
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
|
Placebo
n=30 Participants
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
|
Baseline Hs-CRP of > 3
Participants with a baseline hs-CRP value greater than 3 mg/L.
|
Baseline Hs-CRP of >5 mg/L
Participants with a baseline hs-CRP value greater than 5 mg/L.
|
|---|---|---|---|---|
|
Number of Remitted Patients During Treatment
|
9 participants
|
8 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 1, 2, 4, 6, 8, 10 and 12The Inventory of Depressive Symptomatology-Self-Report (IDS-SR) is a 30-item questionnaire asking respondents about symptoms of depression that they have experienced in the past 7 days. Each item is scored on a 4-point scale where 0 means that the symptom is absent and 3 means that the symptom is very strongly felt. Total scores can range between 0 and 84 and higher scores indicate more severe symptoms of depression.
Outcome measures
| Measure |
Infliximab
n=30 Participants
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
|
Placebo
n=30 Participants
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
|
Baseline Hs-CRP of > 3
Participants with a baseline hs-CRP value greater than 3 mg/L.
|
Baseline Hs-CRP of >5 mg/L
Participants with a baseline hs-CRP value greater than 5 mg/L.
|
|---|---|---|---|---|
|
Inventory of Depressive Symptomatology-Self-Report (IDS-SR) Scores
Baseline
|
43.5 units on a scale
Standard Deviation 9.1
|
43.9 units on a scale
Standard Deviation 9
|
—
|
—
|
|
Inventory of Depressive Symptomatology-Self-Report (IDS-SR) Scores
Week 1
|
37.0 units on a scale
Standard Deviation 13
|
38 units on a scale
Standard Deviation 12
|
—
|
—
|
|
Inventory of Depressive Symptomatology-Self-Report (IDS-SR) Scores
Week 2
|
35.0 units on a scale
Standard Deviation 13
|
36 units on a scale
Standard Deviation 11
|
—
|
—
|
|
Inventory of Depressive Symptomatology-Self-Report (IDS-SR) Scores
Week 4
|
32 units on a scale
Standard Deviation 13
|
32 units on a scale
Standard Deviation 13
|
—
|
—
|
|
Inventory of Depressive Symptomatology-Self-Report (IDS-SR) Scores
Week 6
|
33 units on a scale
Standard Deviation 13
|
33 units on a scale
Standard Deviation 13
|
—
|
—
|
|
Inventory of Depressive Symptomatology-Self-Report (IDS-SR) Scores
Week 8
|
31 units on a scale
Standard Deviation 13
|
29 units on a scale
Standard Deviation 15
|
—
|
—
|
|
Inventory of Depressive Symptomatology-Self-Report (IDS-SR) Scores
Week 10
|
31 units on a scale
Standard Deviation 14
|
30 units on a scale
Standard Deviation 15
|
—
|
—
|
|
Inventory of Depressive Symptomatology-Self-Report (IDS-SR) Scores
Week 12
|
32 units on a scale
Standard Deviation 15
|
29 units on a scale
Standard Deviation 16
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12This study collected blood samples to assess inflammatory markers. IL-6 is a proinflammatory cytokine that is elevated during times of inflammation, infection, illness, and in patients with mood disorders. IL-6 is not present or is low in healthy individuals and exact reference ranges vary by lab, with an example normal reference range of 0.31 to 5.00 picograms per milliliter (pg/mL).
Outcome measures
| Measure |
Infliximab
n=30 Participants
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
|
Placebo
n=30 Participants
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
|
Baseline Hs-CRP of > 3
Participants with a baseline hs-CRP value greater than 3 mg/L.
|
Baseline Hs-CRP of >5 mg/L
Participants with a baseline hs-CRP value greater than 5 mg/L.
|
|---|---|---|---|---|
|
Plasma Concentrations of Interleukin-6 (IL-6)
Baseline IL-6
|
2.04 pg/ml
Standard Deviation 1.6
|
2.13 pg/ml
Standard Deviation 1.19
|
—
|
—
|
|
Plasma Concentrations of Interleukin-6 (IL-6)
Week 12 IL-6
|
1.88 pg/ml
Standard Deviation 2.25
|
1.89 pg/ml
Standard Deviation 1.17
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12This study collected blood samples to assess inflammatory markers. CRP increases when inflammation is present and can be measured with a high sensitivity-CRP (hs-CRP) test. Hs-CRP values \<1 milligram per liter (mg/L) indicate low inflammation while values \>10mg/L indicate inflammation.
Outcome measures
| Measure |
Infliximab
n=30 Participants
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
|
Placebo
n=30 Participants
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
|
Baseline Hs-CRP of > 3
Participants with a baseline hs-CRP value greater than 3 mg/L.
|
Baseline Hs-CRP of >5 mg/L
Participants with a baseline hs-CRP value greater than 5 mg/L.
|
|---|---|---|---|---|
|
Plasma Concentrations of CRP
Baseline hs-CRP
|
6.21 mg/L
Standard Deviation 9.13
|
5.69 mg/L
Standard Deviation 8.17
|
—
|
—
|
|
Plasma Concentrations of CRP
Week 12 hs-CRP
|
3.91 mg/L
Standard Deviation 4.67
|
6.31 mg/L
Standard Deviation 6.92
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: TNF-alpha values were invalid due to the administration of infliximab interfering with processing TNF-alpha.
This study collected blood samples to assess inflammatory markers. Tumor necrosis factor (TNF)-alpha values are invalid due to the administration of infliximab which interferes with the assay procedure.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Week 8Population: This analysis includes participants having complete polysomnography data at baseline and study week 8, and who did not exhibit sleep apnea or periodic limb movement disorder (PLMD).
Sleep efficiency is the percentage of time in bed spent sleeping (total sleep time/sleep period time x 100). A sleep efficiency of 80% or greater is considered normal. This outcome measures examines sleep efficiency between study treatment groups.
Outcome measures
| Measure |
Infliximab
n=19 Participants
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
|
Placebo
n=17 Participants
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
|
Baseline Hs-CRP of > 3
Participants with a baseline hs-CRP value greater than 3 mg/L.
|
Baseline Hs-CRP of >5 mg/L
Participants with a baseline hs-CRP value greater than 5 mg/L.
|
|---|---|---|---|---|
|
Sleep Efficiency
Baseline
|
89.2 percentage of time asleep
Standard Deviation 6.7
|
87.9 percentage of time asleep
Standard Deviation 10.7
|
—
|
—
|
|
Sleep Efficiency
Week 8
|
91.5 percentage of time asleep
Standard Deviation 7.7
|
90.2 percentage of time asleep
Standard Deviation 7.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 8Population: This analysis includes participants having complete polysomnography data at baseline and study week 8, who did not exhibit sleep apnea or {LMD, and who were treated with infliximab.
Sleep efficiency is the percentage of time in bed spent sleeping (total sleep time/sleep period time x 100). A sleep efficiency of 80% or greater is considered normal. This outcome measure examines sleep efficiency between participants with high or low baseline CRP.
Outcome measures
| Measure |
Infliximab
n=9 Participants
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
|
Placebo
n=10 Participants
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
|
Baseline Hs-CRP of > 3
Participants with a baseline hs-CRP value greater than 3 mg/L.
|
Baseline Hs-CRP of >5 mg/L
Participants with a baseline hs-CRP value greater than 5 mg/L.
|
|---|---|---|---|---|
|
Sleep Efficiency in High (CRP>5mg/L) Versus Low (CRP < or =5mg/L) Infliximab-treated Patients
Baseline
|
89.8 percentage of time asleep
Standard Deviation 4.2
|
88.6 percentage of time asleep
Standard Deviation 8.5
|
—
|
—
|
|
Sleep Efficiency in High (CRP>5mg/L) Versus Low (CRP < or =5mg/L) Infliximab-treated Patients
Week 8
|
94.5 percentage of time asleep
Standard Deviation 3.5
|
88.7 percentage of time asleep
Standard Deviation 9.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: This analysis includes all study participants in the first group then progressively limits participants in subsequent groups based on baseline hs-CRP concentrations.
The effects of baseline high-sensitivity C-reactive protein (hs-CRP) on reduction in depressive symptoms were investigated by examining the least squares mean change in the HDRS score from baseline to week 12 (infliximab minus placebo) among participants with baseline CRP of \>1 mg/L, \>3 mg/L, and \>5 mg/L. A negative change score favors infliximab. The HDRS is a 17-item survey asking respondents to rate the degree of depressive symptoms they are feeling on a scale of 0 to 2-4, where 0 means the symptom is absent and 2-4 means the symptom is very strong. Total scores can range from 0 to 52 where higher scores represent greater symptom severity. Scores of 0-7 are considered normal, scores of 8-16 indicates mild depression, scores of 17-23 indicate moderate depression, and scores of 24 and greater indicate severe depression.
Outcome measures
| Measure |
Infliximab
n=60 Participants
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
|
Placebo
n=45 Participants
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
|
Baseline Hs-CRP of > 3
n=27 Participants
Participants with a baseline hs-CRP value greater than 3 mg/L.
|
Baseline Hs-CRP of >5 mg/L
n=22 Participants
Participants with a baseline hs-CRP value greater than 5 mg/L.
|
|---|---|---|---|---|
|
Change in Hamilton Depression Rating Scale 17 (HDRS-17) Scores Subgrouped by Baseline Hs-CRP
|
2.1 score on a scale
Standard Error 1.8
|
0.3 score on a scale
Standard Error 2.1
|
-1.8 score on a scale
Standard Error 2.8
|
-3.1 score on a scale
Standard Error 3.3
|
Adverse Events
Infliximab
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Infliximab
n=30 participants at risk
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
|
Placebo
n=30 participants at risk
Participants receiving normal saline at Baseline, Week 2, and Week 6.
|
|---|---|---|
|
Nervous system disorders
Headache
|
66.7%
20/30 • 12 weeks
regular investigator assessment
|
60.0%
18/30 • 12 weeks
regular investigator assessment
|
|
Respiratory, thoracic and mediastinal disorders
Coughing
|
16.7%
5/30 • 12 weeks
regular investigator assessment
|
16.7%
5/30 • 12 weeks
regular investigator assessment
|
|
Respiratory, thoracic and mediastinal disorders
Sore Throat
|
13.3%
4/30 • 12 weeks
regular investigator assessment
|
20.0%
6/30 • 12 weeks
regular investigator assessment
|
|
Psychiatric disorders
Insomnia
|
16.7%
5/30 • 12 weeks
regular investigator assessment
|
13.3%
4/30 • 12 weeks
regular investigator assessment
|
|
Gastrointestinal disorders
Diarrhea
|
10.0%
3/30 • 12 weeks
regular investigator assessment
|
20.0%
6/30 • 12 weeks
regular investigator assessment
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
13.3%
4/30 • 12 weeks
regular investigator assessment
|
6.7%
2/30 • 12 weeks
regular investigator assessment
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
13.3%
4/30 • 12 weeks
regular investigator assessment
|
6.7%
2/30 • 12 weeks
regular investigator assessment
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
13.3%
4/30 • 12 weeks
regular investigator assessment
|
3.3%
1/30 • 12 weeks
regular investigator assessment
|
|
Psychiatric disorders
Panic attack
|
6.7%
2/30 • 12 weeks
regular investigator assessment
|
10.0%
3/30 • 12 weeks
regular investigator assessment
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.3%
4/30 • 12 weeks
regular investigator assessment
|
3.3%
1/30 • 12 weeks
regular investigator assessment
|
|
Renal and urinary disorders
Increased urinary leukocyte esterase
|
0.00%
0/30 • 12 weeks
regular investigator assessment
|
33.3%
10/30 • 12 weeks
regular investigator assessment
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
13.3%
4/30 • 12 weeks
regular investigator assessment
|
0.00%
0/30 • 12 weeks
regular investigator assessment
|
|
Infections and infestations
Yeast infection
|
10.0%
3/30 • 12 weeks
regular investigator assessment
|
3.3%
1/30 • 12 weeks
regular investigator assessment
|
|
Renal and urinary disorders
Increased urinary white blood cells
|
0.00%
0/30 • 12 weeks
regular investigator assessment
|
10.0%
3/30 • 12 weeks
regular investigator assessment
|
|
General disorders
Fever
|
3.3%
1/30 • 12 weeks
regular investigator assessment
|
3.3%
1/30 • 12 weeks
regular investigator assessment
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place