Trial Outcomes & Findings for Dynamics of Inflammation and Its Blockade on Motivational Circuitry in Depression (NCT NCT03006393)

Last Updated: 2021-11-18

Results Overview

Reward motivation was assessed by a laboratory effort-based decision-making (EBDM) task. On each trial, participants make a choice about expending more or less physical effort (rapid button pressing) in exchange for varying amounts of monetary rewards. Models of subjective value were fit to each participants' data using maximum likelihood estimation and were compared using Bayesian Information Criterion to identify the model that provides the best fit for participants' responses. Discounting functions were based on previous work and include linear, quadratic, hyperbolic, flexible power models. Models considering the potential effects of fatigue and examination of post-scan switching behavior were also evaluated. The best-fitting model from baseline data was applied to look at changes related to infliximab. Reported values reflect a model-derived summary statistic for effort discounting behavior, without a fixed range, where lower values associated with greater motivation.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

42 participants

Primary outcome timeframe

Baseline, Day 14

Results posted on

2021-11-18

Participant Flow

Participants were enrolled at Emory University in Atlanta, Georgia, USA. Enrollment began in August 2016 and all follow up was complete by September 26, 2020.

Participant milestones

Participant milestones
Measure	Infliximab Participants randomized to the infliximab group received one infusion of Infliximab (Remicade) administered intravenously (IV) at 5 mg/kg body weight over a two hour period.	Placebo Participants randomized to the placebo group received one infusion of placebo treatment administered intravenously (IV) over a two hour period.
Overall Study STARTED	21	21
Overall Study COMPLETED	20	18
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Infliximab Participants randomized to the infliximab group received one infusion of Infliximab (Remicade) administered intravenously (IV) at 5 mg/kg body weight over a two hour period.	Placebo Participants randomized to the placebo group received one infusion of placebo treatment administered intravenously (IV) over a two hour period.
Overall Study Withdrawal by Subject	1	1
Overall Study Pregnancy	0	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Dynamics of Inflammation and Its Blockade on Motivational Circuitry in Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Infliximab n=21 Participants Participants randomized to the infliximab group received one infusion of Infliximab (Remicade) administered intravenously (IV) at 5 mg/kg body weight over a two hour period.	Placebo n=21 Participants Participants randomized to the placebo group received one infusion of placebo treatment administered intravenously (IV) over a two hour period.	Total n=42 Participants Total of all reporting groups
Age, Continuous	40.1 years STANDARD_DEVIATION 9.2 • n=5 Participants	38.0 years STANDARD_DEVIATION 7.9 • n=7 Participants	39.03 years STANDARD_DEVIATION 8.53 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	19 Participants n=7 Participants	37 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	12 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) White	13 Participants n=5 Participants	5 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants	21 participants n=7 Participants	42 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Day 14

Population: This analysis includes participants who completed the indicated study visit.

Outcome measures

Outcome measures
Measure	Infliximab n=21 Participants Participants randomized to the infliximab group received one infusion of Infliximab (Remicade) administered intravenously (IV) at 5 mg/kg body weight over a two hour period.	Placebo n=21 Participants Participants randomized to the placebo group received one infusion of placebo treatment administered intravenously (IV) over a two hour period.
Effort-based Decision-making (EBDM) Task Score Day 14	1.85 score on a scale Standard Deviation 1.28	2.78 score on a scale Standard Deviation 1.70
Effort-based Decision-making (EBDM) Task Score Baseline	2.13 score on a scale Standard Deviation 1.76	2.09 score on a scale Standard Deviation 1.52

SECONDARY outcome

Timeframe: Baseline, Day 14

Population: This analysis includes participants who completed the indicated study visit and had usable blood samples. Some participants did not complete the trial and another participant had a blood sample of poor quality.

C-reactive protein (CRP) is a blood test marker for inflammation in the body. CRP is produced in the liver and its level is measured by testing the blood. CRP level was measured at baseline and Day 14. Lower result correlates with better outcome.

Outcome measures

Outcome measures
Measure	Infliximab n=20 Participants Participants randomized to the infliximab group received one infusion of Infliximab (Remicade) administered intravenously (IV) at 5 mg/kg body weight over a two hour period.	Placebo n=21 Participants Participants randomized to the placebo group received one infusion of placebo treatment administered intravenously (IV) over a two hour period.
Plasma C-reactive Protein (CRP) Level Baseline	4.18 mg/L Standard Deviation 3.28	7.81 mg/L Standard Deviation 7.85
Plasma C-reactive Protein (CRP) Level Day 14	2.78 mg/L Standard Deviation 4.63	6.35 mg/L Standard Deviation 6.96

SECONDARY outcome

Timeframe: Baseline, Day 14

Plasma IL-6 level will be collected via blood draw. IL-6 level was collected at baseline and Day 14. Lower result correlates with better outcome.

Outcome measures

Outcome measures
Measure	Infliximab n=20 Participants Participants randomized to the infliximab group received one infusion of Infliximab (Remicade) administered intravenously (IV) at 5 mg/kg body weight over a two hour period.	Placebo n=21 Participants Participants randomized to the placebo group received one infusion of placebo treatment administered intravenously (IV) over a two hour period.
Plasma Interleukin-6 (IL-6) Level Day 14	0.97 pg/ml Standard Deviation 1.00	1.19 pg/ml Standard Deviation 1.25
Plasma Interleukin-6 (IL-6) Level Baseline	1.13 pg/ml Standard Deviation 0.96	1.07 pg/ml Standard Deviation 0.97

Adverse Events

Infliximab

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Michael Treadway

Emory University

Phone: (404) 727-3166

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Infliximab n=21 participants at risk Participants randomized to the infliximab group received one infusion of Infliximab (Remicade) administered intravenously (IV) at 5 mg/kg body weight over a two hour period.	Placebo n=21 participants at risk Participants randomized to the placebo group received one infusion of placebo treatment administered intravenously (IV) over a two hour period.
General disorders Headache	38.1% 8/21 • Number of events 8 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	38.1% 8/21 • Number of events 8 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Gastrointestinal disorders Heartburn	9.5% 2/21 • Number of events 2 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Reproductive system and breast disorders Menstruation	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	9.5% 2/21 • Number of events 2 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Vascular disorders Bruises	23.8% 5/21 • Number of events 5 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	23.8% 5/21 • Number of events 5 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
General disorders Syncope	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Musculoskeletal and connective tissue disorders Pain in joints	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
General disorders Sore throat	19.0% 4/21 • Number of events 4 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Gastrointestinal disorders Bloody stool	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Musculoskeletal and connective tissue disorders Pain in leg	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
General disorders Chills	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
General disorders Allergies	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	9.5% 2/21 • Number of events 2 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
General disorders Dizziness	9.5% 2/21 • Number of events 2 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Gastrointestinal disorders Nausea	9.5% 2/21 • Number of events 2 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
General disorders Chest pain	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Renal and urinary disorders Change in urination	9.5% 2/21 • Number of events 2 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
General disorders Change in blood pressure	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Musculoskeletal and connective tissue disorders Muscle tension	14.3% 3/21 • Number of events 3 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Ear and labyrinth disorders Vertigo	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Skin and subcutaneous tissue disorders Itchiness	9.5% 2/21 • Number of events 2 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	9.5% 2/21 • Number of events 2 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
General disorders Motor vehicle accident	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Musculoskeletal and connective tissue disorders Pain in neck	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Pregnancy, puerperium and perinatal conditions Pregnancy	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Gastrointestinal disorders Stomach ache	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Nervous system disorders Numbness	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
General disorders Fatigue	9.5% 2/21 • Number of events 2 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Nervous system disorders Migraine	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
General disorders Swelling	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	9.5% 2/21 • Number of events 2 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Musculoskeletal and connective tissue disorders Laceration	52.4% 11/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
General disorders Change in appetite	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/21 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.	4.8% 1/21 • Number of events 1 • Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.