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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01MH112076-01 | U.S. NIH Grant/Contract | View source |
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The study was suspended in March 2020 due to the COVID-19 pandemic and ultimately was terminated as it is not safe to test a potent anti-inflammatory drug with ongoing surges of COVID-19.
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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Increased inflammation has been implicated in the pathophysiology of a number of neuropsychiatric illnesses including mood disorders, which affect almost 30 million adults in the United States alone. One mechanism by which inflammation may alter behavior is through increasing brain glutamate, a neurotransmitter that in excess has been implicated in neuronal toxicity and resistance to conventional antidepressant therapy. The goal of the proposed research is to test the hypothesis that inflammation alters behavior through increasing glutamate in specific brain regions, ultimately leading to behavioral changes.
The proposed research is designed to determine the cause and effect relationship between inflammation and CNS glutamate as well as the relationship between CNS glutamate and specific symptoms. To accomplish these aims, investigators will administer a single infusion of either the tumor necrosis factor (TNF) antagonist infliximab or placebo (n=30 per group) to patients with high inflammation (CRP>3mg/L). A CRP>3mg/L was chosen because it is considered high inflammation according to guidelines by the American Heart Association. Moreover, a CRP>3mg/L is associated with significantly increased basal ganglia glutamate and with a clinical response to infliximab. Inflammatory biomarkers, basal ganglia glutamate as measured by MRS, and motivation and psychomotor activity will be assessed at baseline and days 1 and 3 and weeks 1 and 2 following infliximab or placebo administration.
This study aims to test the hypothesis that increased inflammation causes increased basal ganglia glutamate and consequently anhedonia and psychomotor retardation in patients with major depressive disorder (MDD). Excessive inflammation and glutamate excitotoxicity are two pathways that have received increasing attention regarding the pathophysiology of neuropsychiatric disease including mood disorders. Patients with depression exhibit increased peripheral and central nervous system (CNS) markers of inflammation as well as altered CNS glutamate as measured by magnetic resonance spectroscopy (MRS). In addition, drugs that block either inflammation or glutamate signaling can reverse depressive symptoms, especially in depressed patients with treatment resistance.
Inflammatory cytokines are known to inhibit glutamate reuptake and increase glutamate release from astrocytes, and glutamate antagonists have been shown to block inflammation-induced depressive-like behavior in mice. Moreover, using MRS, data has shown that administration of the inflammatory cytokine interferon (IFN)-alpha significantly increases glutamate in the basal ganglia in association with IFN-alpha-induced anhedonia and psychomotor slowing. In addition, increased inflammation as reflected by peripheral blood C-reactive protein (CRP) is correlated with increased basal ganglia glutamate in association with decreased motivation and psychomotor speed in patients with MDD. Nevertheless, the data to date has been correlational, and whether increased inflammation causes increased glutamate in the basal ganglia, which in turn contributes to behavioral changes in patients with depression has not been established.
To test this hypothesis, investigators plan to determine the cause and effect relationship between increased inflammation and increased CNS glutamate by blocking inflammation in depressed patients with high inflammation (CRP>3mg/L) using the highly specific tumor necrosis factor (TNF) antagonist infliximab (n=30) versus placebo (n=30). In addition, the study team will examine whether changes in basal ganglia glutamate are linked to changes in behaviors related to the basal ganglia including anhedonia and psychomotor retardation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Infliximab | Experimental | Participants will be randomized to receive one intravenous (IV) infusion of infliximab. |
|
| Placebo | Placebo Comparator | Participants will be randomized to receive one intravenous (IV) infusion of placebo. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Infliximab | Drug | Infliximab will be administered intravenously (IV) as 5 mg/kg body weight over a 2 to 2.5 hour period. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Central Nervous System (CNS) Glutamate | Left basal ganglia glutamate was measured by magnetic resonance spectroscopy (MRS). Left basal ganglia glutamate tends to be increased during inflammation and is also associated with an increase in depressive symptoms. | Baseline, Day 3, Week 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Snaith-Hamilton Pleasure Scale - Clinician Administered (SHAPS-C) Score | The SHAPS-C is a 14-item, clinician-administered instrument assessing pleasure response/hedonic experience. Responses are scored as 1 = lots of pleasure, 2 = average/usual pleasure, 3 = some pleasure, and 4 = no pleasure. Total scores range from 14 to 56 where higher scores indicate increasing severity of anhedonia. | Baseline, Day 3, Week 2 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Andrew H Miller, MD | Emory University | Principal Investigator |
| Ebrahim Haroon, MD | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University | Atlanta | Georgia | 30322 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30524702 | Derived | Lee Y, Subramaniapillai M, Brietzke E, Mansur RB, Ho RC, Yim SJ, McIntyre RS. Anti-cytokine agents for anhedonia: targeting inflammation and the immune system to treat dimensional disturbances in depression. Ther Adv Psychopharmacol. 2018 Nov 19;8(12):337-348. doi: 10.1177/2045125318791944. eCollection 2018 Dec. |
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Participants were recruited from Emory University Hospitals and Clinics in Atlanta, Georgia, USA. Participant enrollment began May 15, 2017 and the final follow-up assessment occurred November 27, 2019. The study was suspended in March 2020 during the coronavirus disease 2019 (COVID-19) pandemic. Due to the intervention being an immune suppressant it was not safe to reopen the study to enrollment and the decision was made to terminate the study in March 2023.
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| ID | Title | Description |
|---|---|---|
| FG000 | Infliximab | Participants randomized to receive one intravenous (IV) infusion of infliximab. |
| FG001 | Placebo | Participants will be randomized to receive one intravenous (IV) infusion of placebo. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Infliximab | Participants randomized to receive one intravenous (IV) infusion of infliximab. |
| BG001 | Placebo | Participants will be randomized to receive one intravenous (IV) infusion of placebo. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Central Nervous System (CNS) Glutamate | Left basal ganglia glutamate was measured by magnetic resonance spectroscopy (MRS). Left basal ganglia glutamate tends to be increased during inflammation and is also associated with an increase in depressive symptoms. | Eleven distinct participants in the placebo study arm were examined at least one time point but some had a poor signal scan resulting in non-usable data. One participant in the placebo study arm was removed from the study following the baseline assessment. | Posted | Mean | Standard Deviation | mmol/kg | Baseline, Day 3, Week 2 |
|
Information on adverse events was collected beginning at the baseline assessment and continued through the final assessment at Week 2.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Infliximab | Participants randomized to receive one intravenous (IV) infusion of infliximab. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Serotonin syndrome after study completion and after receiving escitalopram | Product Issues | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Venipuncture site bruise | Surgical and medical procedures | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Andrew H. Miller, MD | Emory University | 404-727-8260 | amill02@emory.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 14, 2020 | May 10, 2023 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 23, 2019 | Apr 25, 2023 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D003863 | Depression |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D000069285 | Infliximab |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
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| Placebo | Drug | Saline solution will be administered intravenously over a 2 to 2.5 hour period. |
|
|
| Mood and Pleasure Scale - Self Report (MAP-SR) Score | The Mood and Pleasure Scale is an 18-item self-report inventory that was created to disentangle state-wise motivational and consummatory components of everyday activities over a 24-hour period. Responses are given on a 5-point Likert scale where 0 = no pleasure/not at all and 4 = extreme pleasure/very often. Total scores range from 0 to 72 and higher scores indicate greater motivation and pleasure during everyday activities. | Baseline, Day 3, Week 2 |
| Finger Tapping Task (FTT) Score | The FTT uses a specially adapted tapper that the participant taps as fast as possible using the index finger. The participant is given 5 consecutive 10-second trials for the dominant hands. The finger tapping score is the mean of 5 trials. The FTT is designed to assess subtle motor impairment and is altered in subjects with basal ganglia disorders and lesions. A lower score indicates motor impairment. | Baseline, Day 3, Week 2 |
| Digit Symbol Substitution Task (DSST) Score | The DSST is a subtest of the Wechsler Adult Intelligence Scale (WAIS) and consists of rows of blank squares, each printed with a randomly assigned number. The test involves graphomotor speed, visual scanning and memory, with about half of the variance being accounted for by graphomotor speed, a third by visual scanning and 4-5% by memory. Performance on the DSST has been found to correlate with subcortical atrophy in disorders involving basal ganglia.The DSST is scored as the number of correct responses in 120 seconds, with higher scores indicating better performance. | Baseline, Day 3, Week 2 |
| Trails Making Test A (TMT-A) Score | The scale measures cognitive processing speed using a series of non-sequentially arranged numbers where the participant is asked to sequentially track the numbers occurring to numerical order as quickly as possible. The score is the time time it takes to complete the task, measured in seconds. A longer time to finish may indicate cognitive impairment. | Baseline, Day 3, Week 2 |
| Multidimensional Fatigue Inventory (MFI) Score | The Multidimensional Fatigue Inventory (MFI) is a 20-item self-report instrument designed to measure motivation and fatigue, covering the dimensions of General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation and Reduced Activity. Participants respond to fatigue related statements using a 5-point scale where 1 = "yes, that is true" and 5 = "no, that is not true". Total scores range from 20 to 100 and higher scores indicate greater fatigue. | Baseline, Day 3, Week 2 |
| Inventory of Depressive Symptoms-Clinician Rating (IDS-SR) Score | The Inventory of Depressive Symptomatology-Self-Report (IDS-SR) is a 30-item self-report instrument designed to measure symptom constructs consistent with current Diagnostic and Statistical Manual of Mental Disorders (DSM) nosology and that has been widely used as a self-report outcome measure of depression. Participants complete 28 of the 30 items, depending on if they experienced an increase or decrease in appetite and weight. 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. | Baseline, Day 3, Week 2 |
| Plasma Concentrations of High-sensitivity C-reactive Protein (Hs-CRP) | This study collected blood samples to assess inflammatory markers. Increases in hsCRP are seen when inflammation is present. | Baseline, Day 3, Week 2 |
| Plasma Concentrations of Tumor Necrosis Factor Alpha (TNF-α) | This study collected blood samples to assess inflammatory markers. TNF-α is elevated in patients experiencing inflammation and a decrease in serum TNF-α is an indication of effective treatment. | Baseline, Day 3, Week 2 |
| Plasma Concentrations of Tumor Necrosis Factor (TNF) Receptor 2 (TNFR2) | This study collected blood samples to assess inflammatory markers. TNFR2 has proinflammatory effects and has strong anti-inflammatory activities. | Baseline, Day 3, Week 2 |
| Plasma Concentrations of Interleukin-1 Receptor Antagonist (IL-1Ra) | This study collected blood samples to assess inflammatory markers. IL-1Ra is an anti-inflammatory protein secreted by immune cells, epithelial cells, and adipocytes. | Baseline, Day 3, Week 2 |
| Plasma Concentrations of IL-6 | 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). | Baseline, Day 3, Week 2 |
| Plasma Concentrations of Soluble IL-6 Receptor (sIL-6R) | This study collected blood samples to assess inflammatory markers. Working with the pro-inflammatory cytokine IL-6, sIL-6R regulates pro-inflammatory reactions. | Baseline, Day 3, Week 2 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
Participants will be randomized to receive one intravenous (IV) infusion of placebo. |
|
|
| Secondary | Snaith-Hamilton Pleasure Scale - Clinician Administered (SHAPS-C) Score | The SHAPS-C is a 14-item, clinician-administered instrument assessing pleasure response/hedonic experience. Responses are scored as 1 = lots of pleasure, 2 = average/usual pleasure, 3 = some pleasure, and 4 = no pleasure. Total scores range from 14 to 56 where higher scores indicate increasing severity of anhedonia. | One participant in the placebo study arm was removed from the study following the baseline assessment. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Day 3, Week 2 |
|
|
|
| Secondary | Mood and Pleasure Scale - Self Report (MAP-SR) Score | The Mood and Pleasure Scale is an 18-item self-report inventory that was created to disentangle state-wise motivational and consummatory components of everyday activities over a 24-hour period. Responses are given on a 5-point Likert scale where 0 = no pleasure/not at all and 4 = extreme pleasure/very often. Total scores range from 0 to 72 and higher scores indicate greater motivation and pleasure during everyday activities. | One participant in the infliximab study arm did not complete this assessment at the Day 3 time point. One participant in the placebo study arm was removed from the study following the baseline assessment. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Day 3, Week 2 |
|
|
|
| Secondary | Finger Tapping Task (FTT) Score | The FTT uses a specially adapted tapper that the participant taps as fast as possible using the index finger. The participant is given 5 consecutive 10-second trials for the dominant hands. The finger tapping score is the mean of 5 trials. The FTT is designed to assess subtle motor impairment and is altered in subjects with basal ganglia disorders and lesions. A lower score indicates motor impairment. | One participant in the placebo study arm was removed from the study following the baseline assessment. Some participants did not complete this assessment at the indicated study visits. | Posted | Mean | Standard Deviation | number of taps | Baseline, Day 3, Week 2 |
|
|
|
| Secondary | Digit Symbol Substitution Task (DSST) Score | The DSST is a subtest of the Wechsler Adult Intelligence Scale (WAIS) and consists of rows of blank squares, each printed with a randomly assigned number. The test involves graphomotor speed, visual scanning and memory, with about half of the variance being accounted for by graphomotor speed, a third by visual scanning and 4-5% by memory. Performance on the DSST has been found to correlate with subcortical atrophy in disorders involving basal ganglia.The DSST is scored as the number of correct responses in 120 seconds, with higher scores indicating better performance. | One participant in the placebo study arm was removed from the study following the baseline assessment. Some participants did not complete this assessment at the indicated study visits. | Posted | Mean | Standard Deviation | correct responses | Baseline, Day 3, Week 2 |
|
|
|
| Secondary | Trails Making Test A (TMT-A) Score | The scale measures cognitive processing speed using a series of non-sequentially arranged numbers where the participant is asked to sequentially track the numbers occurring to numerical order as quickly as possible. The score is the time time it takes to complete the task, measured in seconds. A longer time to finish may indicate cognitive impairment. | One participant in the placebo study arm was removed from the study following the baseline assessment. Some participants did not complete this assessment at the indicated study visits. | Posted | Mean | Standard Deviation | seconds | Baseline, Day 3, Week 2 |
|
|
|
| Secondary | Multidimensional Fatigue Inventory (MFI) Score | The Multidimensional Fatigue Inventory (MFI) is a 20-item self-report instrument designed to measure motivation and fatigue, covering the dimensions of General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation and Reduced Activity. Participants respond to fatigue related statements using a 5-point scale where 1 = "yes, that is true" and 5 = "no, that is not true". Total scores range from 20 to 100 and higher scores indicate greater fatigue. | One participant in the placebo study arm was removed from the study following the baseline assessment. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Day 3, Week 2 |
|
|
|
| Secondary | Inventory of Depressive Symptoms-Clinician Rating (IDS-SR) Score | The Inventory of Depressive Symptomatology-Self-Report (IDS-SR) is a 30-item self-report instrument designed to measure symptom constructs consistent with current Diagnostic and Statistical Manual of Mental Disorders (DSM) nosology and that has been widely used as a self-report outcome measure of depression. Participants complete 28 of the 30 items, depending on if they experienced an increase or decrease in appetite and weight. 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. | One participant in the placebo study arm was removed from the study following the baseline assessment. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Day 3, Week 2 |
|
|
|
| Secondary | Plasma Concentrations of High-sensitivity C-reactive Protein (Hs-CRP) | This study collected blood samples to assess inflammatory markers. Increases in hsCRP are seen when inflammation is present. | One participant in the placebo study arm was removed from the study following the baseline assessment. Samples were not obtained for one participant in the Infliximab group at Baseline and for one participant in the Placebo group at Week 2. | Posted | Mean | Standard Deviation | mg/L | Baseline, Day 3, Week 2 |
|
|
|
| Secondary | Plasma Concentrations of Tumor Necrosis Factor Alpha (TNF-α) | This study collected blood samples to assess inflammatory markers. TNF-α is elevated in patients experiencing inflammation and a decrease in serum TNF-α is an indication of effective treatment. | One participant in the placebo study arm was removed from the study following the baseline assessment. Samples were not obtained for one participant in the Infliximab group at Baseline and for one participant in the Placebo group at Week 2. | Posted | Mean | Standard Deviation | pg/mL | Baseline, Day 3, Week 2 |
|
|
|
| Secondary | Plasma Concentrations of Tumor Necrosis Factor (TNF) Receptor 2 (TNFR2) | This study collected blood samples to assess inflammatory markers. TNFR2 has proinflammatory effects and has strong anti-inflammatory activities. | One participant in the placebo study arm was removed from the study following the baseline assessment. Samples were not obtained for one participant in the Infliximab group at Baseline and for one participant in the Placebo group at Week 2. | Posted | Mean | Standard Deviation | pg/mL | Baseline, Day 3, Week 2 |
|
|
|
| Secondary | Plasma Concentrations of Interleukin-1 Receptor Antagonist (IL-1Ra) | This study collected blood samples to assess inflammatory markers. IL-1Ra is an anti-inflammatory protein secreted by immune cells, epithelial cells, and adipocytes. | One participant in the placebo study arm was removed from the study following the baseline assessment. Samples were not obtained for one participant in the Infliximab group at Baseline and for one participant in the Placebo group at Week 2. | Posted | Mean | Standard Deviation | pg/mL | Baseline, Day 3, Week 2 |
|
|
|
| Secondary | Plasma Concentrations of IL-6 | 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). | One participant in the placebo study arm was removed from the study following the baseline assessment. Samples were not obtained for one participant in the Infliximab group at Baseline and for one participant in the Placebo group at Week 2. | Posted | Mean | Standard Deviation | pg/mL | Baseline, Day 3, Week 2 |
|
|
|
| Secondary | Plasma Concentrations of Soluble IL-6 Receptor (sIL-6R) | This study collected blood samples to assess inflammatory markers. Working with the pro-inflammatory cytokine IL-6, sIL-6R regulates pro-inflammatory reactions. | One participant in the placebo study arm was removed from the study following the baseline assessment. Samples were not obtained for one participant in the Infliximab group at Baseline and for one participant in the Placebo group at Week 2. | Posted | Mean | Standard Deviation | pg/mL | Baseline, Day 3, Week 2 |
|
|
|
| Post-Hoc | Plasma Concentrations of IL-1 Beta | This study collected blood samples to assess inflammatory markers. IL-1 Beta is a mediator of the inflammatory response and increased levels are present with a stronger inflammatory stimulus. | One participant in the placebo study arm was removed from the study following the baseline assessment. Samples were not obtained for one participant in the Infliximab group at Baseline and for one participant in the Placebo group at Week 2. | Posted | Mean | Standard Deviation | pg/mL | Baseline, Day 3, Week 2 |
|
|
|
| Post-Hoc | Plasma Concentrations of Monocyte Chemoattractant Protein-1 (MCP-1) | This study collected blood samples to assess inflammatory markers. Elevated levels of MCP-1 are present with several disease conditions including neuroinflammatory diseases. | One participant in the placebo study arm was removed from the study following the baseline assessment. Samples were not obtained for one participant in the Infliximab group at Baseline and for one participant in the Placebo group at Week 2. | Posted | Mean | Standard Deviation | pg/mL | Baseline, Day 3, Week 2 |
|
|
|
| 0 |
| 11 |
| 1 |
| 11 |
| 6 |
| 11 |
| EG001 | Placebo | Participants will be randomized to receive one intravenous (IV) infusion of placebo. | 0 | 11 | 0 | 11 | 8 | 11 |
| Venipuncture stie pain | Surgical and medical procedures | Non-systematic Assessment |
|
| Infusion site pain | Surgical and medical procedures | Non-systematic Assessment |
|
| Vascular access failure | Surgical and medical procedures | Non-systematic Assessment |
|
| Adhesive reaction | Surgical and medical procedures | Non-systematic Assessment |
|
| Fatigue | General disorders | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Shoulder tightness | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Shoulder pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Headache | General disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Lightheadedness | General disorders | Non-systematic Assessment |
|
| Dizziness | General disorders | Non-systematic Assessment |
|
| Puncture site pain | Surgical and medical procedures | Non-systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| External ear pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Parethesia | Nervous system disorders | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Upper respiratory infection | Infections and infestations | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Rhinorrhea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Increased appetite | General disorders | Non-systematic Assessment |
|
| Infusion site irritation | Surgical and medical procedures | Non-systematic Assessment |
|
Not provided
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| D001798 |
| Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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