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A Study of Infliximab for Treatment Resistant Major Depression (Infliximab)

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ClinicalTrials.gov Identifier: NCT00463580
Recruitment Status : Completed
First Posted : April 20, 2007
Results First Posted : May 12, 2014
Last Update Posted : December 4, 2018
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Andrew H Miller, Emory University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Depression
Interventions Drug: Infliximab
Drug: Placebo
Enrollment 60
Recruitment Details Participants were enrolled at Emory University in Atlanta, Georgia. Enrollment began in December 2008 and all participation ended in June 2011.
Pre-assignment Details 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).
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6. Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
Period Title: Overall Study
Started 30 30
Completed 27 28
Not Completed 3 2
Reason Not Completed
Lost to Follow-up             1             0
Schedule conflict             2             0
Medical/psychiatric complications             0             2
Arm/Group Title Infliximab Placebo Total
Hide Arm/Group Description Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6. Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6. Total of all reporting groups
Overall Number of Baseline Participants 30 30 60
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants 30 participants 60 participants
42.5  (8.2) 44.3  (9.4) 43.4  (8.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 60 participants
Female
20
  66.7%
20
  66.7%
40
  66.7%
Male
10
  33.3%
10
  33.3%
20
  33.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 60 participants
White
23
  76.7%
23
  76.7%
46
  76.7%
Black
6
  20.0%
5
  16.7%
11
  18.3%
Other
1
   3.3%
2
   6.7%
3
   5.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 30 participants 30 participants 60 participants
30
 100.0%
30
 100.0%
60
 100.0%
Hamilton Depression Rating Scale-17 item (HDRS-17)   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 30 participants 30 participants 60 participants
24.1  (4.0) 23.6  (3.8) 23.8  (3.9)
[1]
Measure Description: Hamilton Depression Rating Scale-17 item; Minimum score= 0 Maximum score= 54; Higher scores represent greater symptom severity
1.Primary Outcome
Title Hamilton Depression Rating Scale 17 (HDRS-17) Scores
Hide Description 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.
Time Frame Baseline, Weeks 1, 2, 4, 6, 8, 10 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants beginning the study are included in this analysis.
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description:
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: scores on a scale
Baseline 24.1  (4.0) 23.6  (3.8)
Week 1 20.8  (6.7) 20.4  (4.9)
Week 2 18.8  (7.0) 18.3  (6.2)
Week 4 18.8  (6.7) 16.3  (5.7)
Week 6 17.9  (6.2) 16.4  (5.9)
Week 8 17.5  (7.4) 14.8  (6.8)
Week 10 17.4  (8.4) 13.6  (8.3)
Week 12 16.6  (8.4) 14.0  (8.1)
2.Secondary Outcome
Title Number of Participants With a 50% Reduction in Hamilton Depression Rating Scale (HDRS) Scores
Hide Description 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.
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants beginning the study are included in this analysis.
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description:
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
Overall Number of Participants Analyzed 30 30
Measure Type: Number
Unit of Measure: participants
15 15
3.Secondary Outcome
Title Number of Remitted Patients During Treatment
Hide Description 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.
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants beginning the study are included in this analysis.
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description:
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
Overall Number of Participants Analyzed 30 30
Measure Type: Number
Unit of Measure: participants
9 8
4.Secondary Outcome
Title Inventory of Depressive Symptomatology-Self-Report (IDS-SR) Scores
Hide Description The 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.
Time Frame Baseline, Weeks 1, 2, 4, 6, 8, 10 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description:
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 43.5  (9.1) 43.9  (9)
Week 1 37.0  (13) 38  (12)
Week 2 35.0  (13) 36  (11)
Week 4 32  (13) 32  (13)
Week 6 33  (13) 33  (13)
Week 8 31  (13) 29  (15)
Week 10 31  (14) 30  (15)
Week 12 32  (15) 29  (16)
5.Secondary Outcome
Title Plasma Concentrations of Interleukin-6 (IL-6)
Hide Description This 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).
Time Frame Baseline, Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description:
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: pg/ml
Baseline IL-6 2.04  (1.6) 2.13  (1.19)
Week 12 IL-6 1.88  (2.25) 1.89  (1.17)
6.Secondary Outcome
Title Plasma Concentrations of CRP
Hide Description This 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.
Time Frame Baseline, Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description:
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
Overall Number of Participants Analyzed 30 30
Mean (Standard Deviation)
Unit of Measure: mg/L
Baseline hs-CRP 6.21  (9.13) 5.69  (8.17)
Week 12 hs-CRP 3.91  (4.67) 6.31  (6.92)
7.Secondary Outcome
Title Plasma Concentrations of Tumor Necrosis Factor (TNF)-Alpha
Hide Description 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.
Time Frame Baseline, Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
TNF-alpha values were invalid due to the administration of infliximab interfering with processing TNF-alpha.
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description:
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Sleep Efficiency
Hide Description 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.
Time Frame Baseline, Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description:
Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6.
Participants receiving a placebo of normal saline at Baseline, Week 2, and Week 6.
Overall Number of Participants Analyzed 19 17
Mean (Standard Deviation)
Unit of Measure: percentage of time asleep
Baseline 89.2  (6.7) 87.9  (10.7)
Week 8 91.5  (7.7) 90.2  (7.9)
9.Secondary Outcome
Title Sleep Efficiency in High (CRP>5mg/L) Versus Low (CRP < or =5mg/L) Infliximab-treated Patients
Hide Description 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.
Time Frame Baseline, Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title CRP Greater Than 5 mg/L CRP Less Than or Equal to 5 mg/L
Hide Arm/Group Description:
Participants with a baseline CRP measurement of greater than 5 mg/L, who were treated with infliximab.
Participants with a baseline CRP measurement of less than or equal to 5 mg/L, who were treated with infliximab.
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: percentage of time asleep
Baseline 89.8  (4.2) 88.6  (8.5)
Week 8 94.5  (3.5) 88.7  (9.5)
10.Secondary Outcome
Title Change in Hamilton Depression Rating Scale 17 (HDRS-17) Scores Subgrouped by Baseline Hs-CRP.
Hide Description 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.
Time Frame Baseline, Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This analysis includes all study participants in the first group then progressively limits participants in subsequent groups based on baseline hs-CRP concentrations.
Arm/Group Title All Participants Baseline Hs-CRP of >1 mg/L Baseline Hs-CRP of > 3 Baseline Hs-CRP of >5 mg/L
Hide Arm/Group Description:
All study participants are included.
Participants with a baseline hs-CRP value greater than 1 mg/L.
Participants with a baseline hs-CRP value greater than 3 mg/L.
Participants with a baseline hs-CRP value greater than 5 mg/L.
Overall Number of Participants Analyzed 60 45 27 22
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
2.1  (1.8) 0.3  (2.1) -1.8  (2.8) -3.1  (3.3)
Time Frame 12 weeks
Adverse Event Reporting Description regular investigator assessment
 
Arm/Group Title Infliximab Placebo
Hide Arm/Group Description Participants receiving 5mg/kg of Infliximab at Baseline, Week 2, and Week 6. Participants receiving normal saline at Baseline, Week 2, and Week 6.
All-Cause Mortality
Infliximab Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/30 (0.00%)   0/30 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Infliximab Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/30 (0.00%)   0/30 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Infliximab Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   30/30 (100.00%)   30/30 (100.00%) 
Gastrointestinal disorders     
Diarrhea  2  6/30 (20.00%)  3/30 (10.00%) 
Infections and infestations     
Yeast infection  2  1/30 (3.33%)  3/30 (10.00%) 
Musculoskeletal and connective tissue disorders     
Myalgia  2  1/30 (3.33%)  4/30 (13.33%) 
Nervous system disorders     
Headache  1  18/30 (60.00%)  20/30 (66.67%) 
Psychiatric disorders     
Insomnia  2  4/30 (13.33%)  5/30 (16.67%) 
Panic attack  2  3/30 (10.00%)  2/30 (6.67%) 
Renal and urinary disorders     
Increased presence of urinary leukocyte esterase  2  10/30 (33.33%)  0/30 (0.00%) 
Increased urinary white blood cells  2  3/30 (10.00%)  0/30 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Coughing  1  5/30 (16.67%)  5/30 (16.67%) 
Sore Throat  2  6/30 (20.00%)  4/30 (13.33%) 
Upper respiratory infection  2  2/30 (6.67%)  4/30 (13.33%) 
Nasal congestion  2  2/30 (6.67%)  4/30 (13.33%) 
Sinus congestion  2  0/30 (0.00%)  4/30 (13.33%) 
Skin and subcutaneous tissue disorders     
Rash  2  1/30 (3.33%)  4/30 (13.33%) 
1
Term from vocabulary, Medra
2
Term from vocabulary, MedDRA (Unspecified)
Indicates events were collected by systematic assessment
This study was underpowered to adequately test placebo response typically reported for treatment resistant depression. Also, no direct measures of the effect of either infliximab or placebo on the central nervous system (CNS) were obtained.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Andrew H. Miller
Organization: Emory University
Phone: 404-727-8260
Responsible Party: Andrew H Miller, Emory University
ClinicalTrials.gov Identifier: NCT00463580     History of Changes
Other Study ID Numbers: IRB00011734
1R21MH077172-01A2 ( U.S. NIH Grant/Contract )
First Submitted: April 19, 2007
First Posted: April 20, 2007
Results First Submitted: August 13, 2013
Results First Posted: May 12, 2014
Last Update Posted: December 4, 2018