Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Lupus Research Alliance | OTHER |
Not provided
Not provided
Not provided
Not provided
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease. Joint and muscle pain and fatigue are extremely common among patients and contribute to a reduced quality of life. Available therapies may be associated with significant side effects and many patients do not achieve an adequate response to these treatments. Therefore, there is an unmet need to develop new strategies to reduce pain and fatigue. Filling this need would significantly improve patients' quality of life. This trial will evaluate the effects of a novel approach, stimulating the vagus nerve, a nerve originating in the brain as a potential therapeutic intervention for treatment of musculoskeletal pain and fatigue. Vagus nerve stimulation has multiple beneficial effects and is one of the body's own ways to modulate the immune system. One can stimulate the vagus nerve via the skin at the neck or at specific locations in the ear, (transcutaneous vagus nerve stimulation: tcVNS). We recently completed a short, small scale randomized, placebo controlled trial of tcVNS in patients with SLE and observed dramatic benefits on musculoskeletal pain and fatigue. The treatment was safe without side effects. We are therefore proposing a longer trial to validate our initial findings and to look at durability. In this study, 18 patients with musculoskeletal pain will be followed for 2 months and will receive tcVNS or placebo (sham stimulation) for 5 minutes/day for 28 days. Patients will have a 1 out of 3 chance of receiving sham stimulation and neither the patient nor the evaluating investigator will know the actual treatment. The stimulations are self-administered, are non-painful and have not been associated with serious risks. After 28 days of stimulation, treatment will be discontinued and patients will be monitored for an additional 28 days to evaluate durability. Pain, fatigue and disease activity will be evaluated as well as possible side effects will be monitored throughout the trial. This study will also explore biologic mechanisms that may be responsible for the potential clinical effects. This will include possible effects of stimulation on gut permeability and the stool microbiome, areas that may play a significant role contributing to SLE disease and its manifestations. The development of an effective treatment without significant side effects would be extremely valuable and a significant advance for patients with SLE. If efficacious, tcVNS offers a non-toxic, non-immunosuppressive strategy to control two of the most common symptoms of this disease.
Musculoskeletal (MS) pain and fatigue are common symptoms of patients with Systemic Lupus Erythematosus (SLE) affecting up to 95% and contributing to a reduced quality of life. Safe and efficacious treatment remains an unmet need for these disease manifestations. Stimulation of the vagus nerve results in beneficial effects in patients. We recently completed a short , small scale, randomized, sham-controlled, double blind clinical trial of transcutaneous vagus nerve stimulation (taVNS) in patients with SLE. The clinical benefit on MS pain and fatigue was dramatic. We now propose a randomized sham controlled clinical trial assessing the efficacy and durability of a longer exposure to taVNS (28 days in comparison to the 4 day exposure in the previous trial) in 18 patients randomized 2: 1 with musculoskeletal pain. After 28 days of stimulation, the treatment will be discontinued and patients will be monitored for an additional 28 days to evaluate the treatment's durability. Pain, fatigue, disease activity (global and musculoskeletal) and safety will be evaluated and safety will be monitored throughout the trial. In this clinical trial we will also explore potential biologic mechanisms and pathways by which taVNS exerts ifs effects in SLE, including potential effects on gut permeability and the microbiome.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vagus Nerve Stimulation | Active Comparator | Patients will receive transcutaneous stimulation of the left vagus nerve for 5 minutes daily for 28 consecutive days. |
|
| Sham Vagus Nerve Stimulation | Placebo Comparator | Patients will receive sham transcutaneous stimulation of the of the left vagus nerve for 5 minutes daily for 28 consecutive days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Active vagus nerve stimulation | Device | Patients will receive transcutaneous stimulation of the vagus nerve for 5 minutes daily for 28 consecutive days. The device is a handheld electrical pulse generator and a pair of electrodes will be placed on the skin for stimulation. The electrical pulse generator is turned on and the amplitude of stimulation increased to the greatest amount tolerated. Patients will be followed through day 57 to assess durability of the intervention. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Musculoskeletal Pain From Baseline. | Patients rate their musculoskeletal pain by making a mark on a 10cm anchored Visual Analog Scale where 0=no musculoskeletal pain and 10 =worst possible musculoskeletal pain. | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Subjects With Treatment Emergent Adverse Events. | The percentage of participants with grade 2 or higher or specific grade 1 treatment emergent adverse events will be assessed using the NCI-CTAEversion4. The percentage of participants with grade 2 or higher treatment emergent adverse events will be assessed using the NCI-CTAEversion4. The percentage of participants with grade 2 or higher treatment emergent adverse events will be assessed using the NCI-CTAEversion4. |
| Measure | Description | Time Frame |
|---|---|---|
| Functional gut permeability | Functional gut permeability is assessed by measuring urinary C mannitol/lactulose ratios after oral injestion of the sugars, in timed urine collections over 24 hours. | Day 28 |
| Stool microbiome |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sanita Kandasami | Contact | 516 562-2401 | skandasami@northwell.edu | |
| Cynthia Aranow, MD | Contact | 516 562-3845 | caranow@northwell.edu |
| Name | Affiliation | Role |
|---|---|---|
| Cynthia Aranow, MD | Northwell Health | Principal Investigator |
Not provided
IPD will be shared with researchers with a proposals directed to caranow@northwell.edu. IPD data collected during the trial, after deidentification hat underlie results in a publication will be shared and will be available by 6 months to 3 years following publication of the manuscript.
gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website
6 months to 3 years after publication
Data will be available to researchers who provide a methodologically sound proposal and/or whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.
Not provided
Not provided
| ID | Term |
|---|---|
| D008180 | Lupus Erythematosus, Systemic |
| D010146 | Pain |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Sham vagus nerve stimulation | Device | Patients will receive transcutaneous stimulation of the vagus nerve for 5 minutes daily for 28 consecutive days. The device is a handheld electrical pulse generator and a pair of electrodes will be placed on the skin for stimulation. The electrical pulse generator is turned on and the amplitude of stimulation increased to the greatest amount tolerated, however, the vagus nerve will not be stimulated. Patients will be followed through day 57 to assess durability of the intervention. |
|
| 57 days |
| Change in Musculoskeletal Pain From Baseline | Patients rate their musculoskeletal pain by making a mark on a 10cm anchored Visual Analog Scale where 0=no musculoskeletal pain and 10 =worst possible musculoskeletal pain. | 5 days |
| Change in Musculoskeletal Pain From Baseline | Patients rate their musculoskeletal pain by making a mark on a 10cm anchored Visual Analog Scale where 0=no musculoskeletal pain and 10 =worst possible musculoskeletal pain. | 57 days |
| Change in Musculoskeletal Pain From Day 29 to Day 57 | Patients rate their musculoskeletal pain by making a mark on a 10cm anchored Visual Analog Scale where 0=no musculoskeletal pain and 10 =worst possible musculoskeletal pain. | day 29 to day 57 |
| Fatigue | Change from baseline fatigue will be measured using the FACIT F (Functional Assessment of Chronic Illness Therapy) questionnaire. The score ranges from 0 to 52, a higher score indicates less fatigue. | 5 days |
| Fatigue | Change from baseline fatigue will be measured using the FACIT F (Functional Assessment of Chronic Illness Therapy) questionnaire. The score ranges from 0 to 52, a higher score indicates less fatigue. | 28 days |
| Fatigue | Change from baseline fatigue will be measured using the FACIT F (Functional Assessment of Chronic Illness Therapy) questionnaire. The score ranges from 0 to 52, a higher score indicates less fatigue. | 57 days |
| Fatigue | Change from Day 29 fatigue to Day 57 will be measured using the FACIT F (Functional Assessment of Chronic Illness Therapy) questionnaire. The score ranges from 0 to 52, a higher score indicates less fatigue. | day 29 to day 57 |
| Tender Joint Reduction | The percentage of tender joints reduced from baseline assessed by an investigator upon examining 68 potential tender joints. | 5 days |
| Tender Joint Reduction | The percentage of tender joints reduced from baseline assessed by an investigator upon examining 68 potential tender joints. | 28 days |
| Tender Joint Reduction | The percentage of tender joints reduced from baseline assessed by an investigator upon examining 68 potential tender joints. | 57 days |
| Tender Joint Reduction | The percentage of tender joints reduced from day 29 to day 57 will be assessed by an investigator upon examining 68 potential tender joints. | Day 29 to Day 57 |
| Swollen joint reduction | The percentage of swollen joints reduced from baseline assessed by an investigator upon examining 66 potential swollen joints. Data shown for seven taVNS and five SS subjects with swollen joints at baseline. | 5 days |
| Swollen joint reduction | The percentage of swollen joints reduced from baseline assessed by an investigator upon examining 66 potential swollen joints. Data shown for seven taVNS and five SS subjects with swollen joints at baseline. | 28 days |
| Swollen joint reduction | The percentage of swollen joints reduced from baseline assessed by an investigator upon examining 66 potential swollen joints. Data shown for seven taVNS and five SS subjects with swollen joints at baseline. | 57 days |
| Swollen joint reduction | The percentage of swollen joints reduced from Day 29 to Day 57 assessed by an investigator upon examining 66 potential swollen joints. Data shown for seven taVNS and five SS subjects with swollen joints at baseline. | Day 29 to Day 57 |
| Physician Global Assessment of Disease Activity (PGA) | Change in PGA from baseline, an anchored visual analog scale.ranging from 0 to 3 with higher scores signifying higher disease activity. | Day 5 |
| Physician Global Assessment of Disease Activity (PGA) | Change in PGA from baseline, an anchored visual analog scale.ranging from 0 to 3 with higher scores signifying higher disease activity. | Day 28 |
| Physician Global Assessment of Disease Activity (PGA) | Change in PGA from baseline, an anchored visual analog scale.ranging from 0 to 3 with higher scores signifying higher disease activity. | Day 57 |
| Physician Global Assessment of Disease Activity (PGA) | Change in PGA from day 29 to day 57; PGA is an anchored visual analog scale.ranging from 0 to 3 with higher scores signifying higher disease activity. | Days 29 to 57 |
| Patient Global Assessment of Disease (PtGA) | Change in PtGA from baseline, an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher disease activity. | Day 5 |
| Patient Global Assessment of Disease (PtGA) | Change in PtGA from baseline, an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher disease activity. | Day 28 |
| Patient Global Assessment of Disease (PtGA) | Change in PtGA from baseline, an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher disease activity. | Day 57 |
| Patient Global Assessment of Disease (PtGA) | Change in PtGA from day 29 to 57; PtGA is an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher disease activity. | Days 29 to 57 |
| Pain intensity | Pain intensity assessed by the PROMIS Pain Intensity Form 1a which asks subjects to mark a scale rating the average pain intensity over the past 7 days. The rating scale consists of whole numbers from 1 to 10. The PROMIS Pain Intensity Scale is a series of 3 questions that assess pain intensity at its worst, at its average, and at current moment. A higher score indicates higher levels of pain intensity. | 5 days |
| Pain intensity | Pain intensity assessed by the PROMIS Pain Intensity Form 1a which asks subjects to mark a scale rating the average pain intensity over the past 7 days. The rating scale consists of whole numbers from 1 to 10. The PROMIS Pain Intensity Scale is a series of 3 questions that assess pain intensity at its worst, at its average, and at current moment. A higher score indicates higher levels of pain intensity. | 28 days |
| Pain intensity | Pain intensity assessed by the PROMIS Pain Intensity Form 1a which asks subjects to mark a scale rating the average pain intensity over the past 7 days. The rating scale consists of whole numbers from 1 to 10. The PROMIS Pain Intensity Scale is a series of 3 questions that assess pain intensity at its worst, at its average, and at current moment. A higher score indicates higher levels of pain intensity. | 57 days |
| Pain intensity | Pain intensity assessed by the PROMIS Pain Intensity Form 1a which asks subjects to mark a scale rating the average pain intensity over the past 7 days. The rating scale consists of whole numbers from 1 to 10. The PROMIS Pain Intensity Scale is a series of 3 questions that assess pain intensity at its worst, at its average, and at current moment. A higher score indicates higher levels of pain intensity. | Days 29 to 57 |
| Pain interference | Pain interference will be assessed by requesting subjects to answer the PROMIS Pain Interference Short Form 8a. The PROMIS Pain Interference Short Form 8a is a series of 8 questions which asks how much has pain interfered with different aspects of activities of daily living over the previous 7 days | 5 days |
| Pain interference | Pain interference will be assessed by requesting subjects to answer the PROMIS Pain Interference Short Form 8a. The PROMIS Pain Interference Short Form 8a is a series of 8 questions which asks how much has pain interfered with different aspects of activities of daily living over the previous 7 days | 28 days |
| Pain interference | Pain interference will be assessed by requesting subjects to answer the PROMIS Pain Interference Short Form 8a. The PROMIS Pain Interference Short Form 8a is a series of 8 questions which asks how much has pain interfered with different aspects of activities of daily living over the previous 7 days | 57 days |
| Pain interference | Pain interference will be assessed by requesting subjects to answer the PROMIS Pain Interference Short Form 8a. The PROMIS Pain Interference Short Form 8a is a series of 8 questions which asks how much has pain interfered with different aspects of activities of daily living over the previous 7 days | Days 29 to 57 |
| Health Related Quality of Life (HRQoL)) | HRQoL will be evaluated using the LupusQoL, a validated SLE specific index which assesses 8 domains including physical health, emotional health, body image, pain, planning, fatigue, intimate relationships, and burden to others. Higher scores correspond to worse quality-of-life. | 28 days |
| Health Related Quality of Life (HRQoL)) | HRQoL will be evaluated using the LupusQoL, a validated SLE specific index which assesses 8 domains including physical health, emotional health, body image, pain, planning, fatigue, intimate relationships, and burden to others. Higher scores correspond to worse quality-of-life. | Day 57 |
| Health Related Quality of Life (HRQoL)) | HRQoL will be evaluated using the LupusQoL, a validated SLE specific index which assesses 8 domains including physical health, emotional health, body image, pain, planning, fatigue, intimate relationships, and burden to others. Higher scores correspond to worse quality-of-life. | Days 29 to 57 |
| Anxiety | Promis Anxiety Short Form will assess anxiety. It is an 8 item questionaire assessing components related to anxiety including fear, anxious misery, hyperarousal, and somatic symptoms. Higher scores indicate greater levels of anxiety. | Day 29 |
| Anxiety | Promis Anxiety Short Form will assess anxiety. It is an 8 item questionaire assessing components related to anxiety including fear, anxious misery, hyperarousal, and somatic symptoms. Higher scores indicate greater levels of anxiety. | Day 57 |
| Anxiety | Promis Anxiety Short Form will assess anxiety. It is an 8 item questionaire assessing components related to anxiety including fear, anxious misery, hyperarousal, and somatic symptoms. Higher scores indicate greater levels of anxiety. | Days 29 to 57 |
| Depression | Beck Depression Inventory (BDI) will assess depression. The BDI is a 21 item questionnaire measuring the severity of depression. Higher scores indicate greater levels of depression. | Day 28 |
| Depression | Beck Depression Inventory (BDI) will assess depression. The BDI is a 21 item questionnaire measuring the severity of depression. Higher scores indicate greater levels of depression. | Day 57 |
| Depression | Beck Depression Inventory (BDI) will assess depression. The BDI is a 21 item questionnaire measuring the severity of depression. Higher scores indicate greater levels of depression. | Days 29 to 57 |
| Polysymptomatic distress | Polysymptomatic distress will be assessed by the Fibromyalgia Symptom Score (FSS), a patient reported outcome measuring the extent of polysymptomatic distress on a scale ranging from 0-31. Higher scores correspond to greater polysymptomatic distress. | Day 29 |
| Polysymptomatic distress | Polysymptomatic distress will be assessed by the Fibromyalgia Symptom Score (FSS), a patient reported outcome measuring the extent of polysymptomatic distress on a scale ranging from 0-31. Higher scores correspond to greater polysymptomatic distress. | Day 57 |
| Polysymptomatic distress | Polysymptomatic distress will be assessed by the Fibromyalgia Symptom Score (FSS), a patient reported outcome measuring the extent of polysymptomatic distress on a scale ranging from 0-31. Higher scores correspond to greater polysymptomatic distress. | Days 29 to 57 |
| Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) | SLEDAI-2K is a 24 item index which are scored by an investigator as either present or absent. Items include clinical and laboratory features of SLE. Higher scores correspond to greater disease activity. | Day 28 |
| Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) | SLEDAI-2K is a 24 item index which are scored by an investigator as either present or absent. Items include clinical and laboratory features of SLE. Higher scores correspond to greater disease activity. | Day 57 |
| Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) | SLEDAI-2K is a 24 item index which are scored by an investigator as either present or absent. Items include clinical and laboratory features of SLE. Higher scores correspond to greater disease activity. | Days 29 to 57 |
| BILAG (British Isles Lupus Assessment Group) 2004 | BILAG 2004 index assesses SLE disease activity in nine organ symptoms. Each domain is categorized into 1 of 5 levels (A, B, C, D, E). Lower letters (e.g. A) indicate more active disease. | Day 28 |
| BILAG (British Isles Lupus Assessment Group) 2004 | BILAG 2004 index assesses SLE disease activity in nine organ symptoms. Each domain is categorized into 1 of 5 levels (A, B, C, D, E). Lower letters (e.g. A) indicate more active disease. | Day 57 |
| BILAG (British Isles Lupus Assessment Group) 2004 | BILAG 2004 index assesses SLE disease activity in nine organ symptoms. Each domain is categorized into 1 of 5 levels (A, B, C, D, E). Lower letters (e.g. A) indicate more active disease. | Days 29 to 57 |
| CLASI (Cutaneous LE Disease Area and Severity Index) | CLASI assesses SLE skin disease activity and damage. Higher scores indicate greater levels of cutaneous disease. | Day 28 |
| CLASI (Cutaneous LE Disease Area and Severity Index) | CLASI assesses SLE skin disease activity and damage. Higher scores indicate greater levels of cutaneous disease. | Day 57 |
| CLASI (Cutaneous LE Disease Area and Severity Index) | CLASI assesses SLE skin disease activity and damage. Higher scores indicate greater levels of cutaneous disease. | Days 29 to 57 |
| Musculoskeletal disease activity--patient | Musculoskeletal disease activity will be assessed by patients by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher musculoskeletal disease activity. | Day 5 |
| Musculoskeletal disease activity--patient | Musculoskeletal disease activity will be assessed by patients by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher musculoskeletal disease activity. | Day 29 |
| Musculoskeletal disease activity--patient | Musculoskeletal disease activity will be assessed by patients by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher musculoskeletal disease activity. | Day 57 |
| Musculoskeletal disease activity--patient | Musculoskeletal disease activity will be assessed by patients by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher musculoskeletal disease activity. | Days 29 to 57 |
| Musculoskeletal disease activity--physician | Musculoskeletal disease activity will be assessed by the physician investigator by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher musculoskeletal disease activity. | Day 5 |
| Musculoskeletal disease activity--physician | Musculoskeletal disease activity will be assessed by the physician investigator by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher musculoskeletal disease activity. | Day 28 |
| Musculoskeletal disease activity--physician | Musculoskeletal disease activity will be assessed by the physician investigator by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher musculoskeletal disease activity. | Day 57 |
| Musculoskeletal disease activity--physician | Musculoskeletal disease activity will be assessed by the physician investigator by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying higher musculoskeletal disease activity. | Days 28 to 57 |
| Morning Stiffness | Morning stiffness will be assessed by patients by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying greater morning stiffness. | Day 5 |
| Morning Stiffness | Morning stiffness will be assessed by patients by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying greater morning stiffness. | Day 28 |
| Morning Stiffness | Morning stiffness will be assessed by patients by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying greater morning stiffness. | Day 57 |
| Morning Stiffness | Morning stiffness will be assessed by patients by an anchored visual analog scale.ranging from 0 to 10 with higher scores signifying greater morning stiffness. | Days 29 to 57 |
| Patient assessment of response | Patient assessment of response will be determined by a 5 component Likert scale by the patient. | Day 5 |
| Patient assessment of response | Patient assessment of response will be determined by a 5 component Likert scale by the patient. | Day 28 |
| Patient assessment of response | Patient assessment of response will be determined by a 5 component Likert scale by the patient. | Day 57 |
| Physician assessment of response | Patient assessment of response will be determined by a 5 component Likert scale by the physician investigator. | Day 5 |
| Physician assessment of response | Patient assessment of response will be determined by a 5 component Likert scale by the physician investigator. | Day 28 |
| Physician assessment of response | Patient assessment of response will be determined by a 5 component Likert scale by the physician investigator. | Day 57 |
| Lupus Low Disease Activity State (LLDAS) | LLDAS is a state achieved when there are minimal signs or symptoms of lupus disease activity while the patient is on low dose corticosteroids and stable therapy. | Day 28 |
| Lupus Low Disease Activity State (LLDAS) | LLDAS is a state achieved when there are minimal signs or symptoms of lupus disease activity while the patient is on low dose corticosteroids and stable therapy. | Day 57 |
| SRI-4 | SRI-4 is a composite categorical response measure of improvement in SLE disease activity from a comparator timepoint/baseline. Achievement of the SRI-4 indicates a clinically meaningful response. | Day 28 |
| SRI-4 | SRI-4 is a composite categorical response measure of improvement in SLE disease activity from a comparator timepoint/baseline. Achievement of the SRI-4 indicates a clinically meaningful response. | Day 57 |
Stool microbiome is assessed by determining changes in metagenomics, metatranscriptomics and metabolomics from baseline in stool specimens.
| Day 28 |
| Gut permeability: serum I-FABP, zonulin and LPS, and by stool calprotectin and zonulin | Gut permeability: serum I-FABP is determined by measuring levels of serum I-FABP | Day 28 |
| Gut permeability: zonulin | Gut permeability: zonulin is determined by measuring levels of serum zonulin | Day 28 |
| Gut permeability: Lipopolysaccharide (LPS) | Gut permeability: Lipopolysaccharide (LPS) is determined by measuring levels of serum LPS. | Day 28 |
| Gut permeability: Stool calprotectin | Gut permeability: Stool calprotectin is determined by measuring levels of calprotectin in the stool. | Day 28 |
| Gut permeability: Stool zonulin | Gut permeability: Stool zonulin is determined by measuring levels of zonulin in the stool. | Day 28 |
| Oxidative stress | Oxidative stress is determined by measuring levels of circulating glutathione and oxidized glutathione | Day 28 |
| Oxidative stress | Oxidative stress is determined by measuring levels of circulating glutathione and oxidized glutathione | Day 57 |
| Neurotrophins | Neurotrophins are determined by measuring circulating levels of neurotrophins (nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). | Day 28 |
| Neurotrophins | Neurotrophins are determined by measuring circulating levels of neurotrophins (nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). | Day 57 |
| Neurotrophins | Neurotrophins are determined by measuring circulating levels of neurotrophins (nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). | Days 29 to 57 |
| Kynurenine pathway metabolites | Kynurenine pathway metabolites are determined by measuring circulating levels of tryptophan, kynurenine, kynurenic acid and quinolinic acid | Day 28 |
| Kynurenine pathway metabolites | Kynurenine pathway metabolites are determined by measuring circulating levels of tryptophan, kynurenine, kynurenic acid and quinolinic acid | Day 57 |
| Kynurenine pathway metabolites | Kynurenine pathway metabolites are determined by measuring circulating levels of tryptophan, kynurenine, kynurenic acid and quinolinic acid | Days 28 to 57 |
| Neuropeptides | Neuropeptides are determined by measuring circulating levels of substance P, calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY), neuropeptide B (NPB) and neuropeptide W (NPW). | Day 28 |
| Neuropeptides | Neuropeptides are determined by measuring circulating levels of substance P, calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY), neuropeptide B (NPB) and neuropeptide W (NPW). | Day 57 |
| Neuropeptides | Neuropeptides are determined by measuring circulating levels of substance P, calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY), neuropeptide B (NPB) and neuropeptide W (NPW). | Days 29 to 57 |
| Erythrocyte Sedimentation Rate (ESR) | ESR is a laboratory parameter reflecting inflammation. It measures the rate that erythrocytes sediment (fall) over a specific period of time. | Day 5 |
| Erythrocyte Sedimentation Rate (ESR) | ESR is a laboratory parameter reflecting inflammation. It measures the rate that erythrocytes sediment (fall) over a specific period of time. | Day 28 |
| Erythrocyte Sedimentation Rate (ESR) | ESR is a laboratory parameter reflecting inflammation. It measures the rate that erythrocytes sediment (fall) over a specific period of time. | Day 57 |
| Erythrocyte Sedimentation Rate (ESR) | ESR is a laboratory parameter reflecting inflammation. It measures the rate that erythrocytes sediment (fall) over a specific period of time. | Days 28 to 57 |
| Complement component 3 (C3) | Serum levels of C3 are measured in a clinical laboratory | Day 28 |
| Complement component 3 (C3) | Serum levels of C3 are measured in a clinical laboratory | Day 57 |
| Complement component 3 (C3) | Serum levels of C3 are measured in a clinical laboratory | Days 28 to 57 |
| Complement component 4 (C4) | Serum levels of C4 are measured in a clinical laboratory | Day 28 |
| Complement component 4 (C4) | Serum levels of C4 are measured in a clinical laboratory | Day 57 |
| Complement component 4 (C4) | Serum levels of C4 are measured in a clinical laboratory | Days 28 to 57 |
| Anti-DNA antibodies | Serum levels of anti-DNA antibodies are measured by a laboratory | Day 28 |
| Anti-DNA antibodies | Serum levels of anti-DNA antibodies are measured by a laboratory | Day 57 |
| Anti-DNA antibodies | Serum levels of anti-DNA antibodies are measured by a laboratory | Days 28 to 57 |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |