Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Idiopathic Parkinson's Disease

Parkinson's Disease Clinical Trial

Official title:

Pilot Phase I Study of Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Idiopathic Parkinson's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02611167
• Other study ID #: HSC-MS-16-0026
• Status: Completed
• Phase: Phase 1
• Start date: November 1, 2017
• Est. completion date: September 18, 2019

Study information

• Verified date: November 2023
• Source: The University of Texas Health Science Center, Houston
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety, feasibility, and efficacy of intravenous allogeneic bone marrow-derived mesenchymal stem cell (MSC) therapy for idiopathic Parkinson's disease (iPD).

Description:

Allogeneic bone marrow-derived mesenchymal stem cells (MSCs) will be delivered intravenously at one of four doses: 1 x 10 6 MSC/kg, 3 x 10 6 MSC/kg, 6 x 10 6 MSC/kg, or 10 x 10 6 MSC/kg of body weight to a population of patients with idiopathic Parkinson's disease (iPD). The infusion will be at 1 week after the baseline visit, following two screening visits. Patients will be followed until 52 weeks after the infusion visit. The safety of the therapy, as well as the impact of the therapy on the rate of Parkinson's disease (PD) progression, will be assessed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: September 18, 2019
• Est. primary completion date: September 18, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 70 Years

Eligibility

Inclusion Criteria:

• Men and women between the ages of 45 and 70. The 45-year-old age cutoff ensures that we do not enroll juvenile PD patients.

• Diagnosis of Parkinson disease by the United Kingdom (UK) brain bank criteria including the presence of 2 cardinal signs of PD plus bradykinesia. Diagnosis will be confirmed by the PI or other specialists in Movement Disorders and based on medical history, physical and neurological exams. Patients should have an asymmetric onset, unilateral symptoms and a negative pull test. (See Appendix A)

• Moderate to severe microsmia (UPSIT <29).

• A modified Hoehn and Yahr stage of 3 or less in the levodopa OFF state. (See Appendix B)

• Diagnosis of PD between 4 to 7 years.

• Robust response to dopaminergic therapy (defined as greater than 33% reduction in symptoms (on the Unified Parkinson's Disease Rating Scale; UPDRS) when measured in the ON medicine state compared to OFF state.

• If subject is taking any central nervous system acting medications (e.g., benzodiazepines, antidepressants, hypnotics) regimen must be optimized and stable for 90 days prior to the screening visit.

• A stable Parkinson's disease symptomatic therapy for at least 90 days prior to screening and not projected to require additional Parkinson's disease symptomatic therapy for at least one year from the baseline visit.

• Women of childbearing potential will be required to use a reliable form of contraception from 30 days prior to baseline visit until 6 months after the final dose of the study drug.

Exclusion Criteria:

• Atypical or drug-induced Parkinsonism.

• A UPDRS rest tremor score of 3 or greater for any limb.

• A Montreal Cognitive Assessment (MoCA) score of less than 25. (See Appendix C)

• Clinical features of psychosis or refractory hallucinations.

• Uncontrolled seizure disorder, defined as a seizure within the last 6 months.

• Developmental delay.

• Chronic kidney disease defined as glomerular filtration rate (GFR) < 50 mL/min/m2.

• Hepatic disease or altered liver function as defined by alanine transaminase (ALT) >150 U/L and or T. Bilirubin >1.6 mg/dl at admission.

• Presence of clinically refractory orthostatic hypotension at the screening or baseline visit defined as greater than or equal to 20 mmHg change in systolic BP and greater than or equal to 10 mmHg change in diastolic BP from sitting position to standing after 2 minutes that does not respond to medical treatment or baseline sitting BP less than 90/60.

• History of congestive heart failure, clinically significant bradycardia, presence of 2nd or 3rd degree atrioventricular block.

• Pulmonary disease: chronic obstructive pulmonary disease (COPD) with oxygen-requirement at rest or with ambulation; or moderate to severe asthma.

• Active malignancy or diagnosis of malignancy within 5 years prior to the start of screening (Cancer free for at least 5 years is permitted; skin cancers, except for melanoma, are permitted).

• Any diagnosis of autoimmune disease or immunocompromised state, including chemotherapy administration within last 3 years or current immunosuppression as defined by white blood cell (WBC) <3 x 103 cells/ml.

• History of strokes or traumatic brain injury.

• Major surgery within the previous 3 months or planned in the ensuing 6 months.

• Clinically significant abnormalities in the Screening Visit laboratory studies.

• History of use of an investigational drug within 30 days prior to the screening visit.

• History of brain surgery for PD.

• Unable to return for follow-up visits for clinical evaluation, laboratory studies, or imaging evaluation.

• Substance abuse disorder.

• Active anticoagulation treatment.

• Any other condition that the investigator feels would pose a significant hazard to the patient if enrolled or complicate the study assessments.

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Biological:
• Allogeneic bone marrow-derived MSCs (1 x 10 6 MSC/kg)
Bone marrow-derived allogeneic MSCs will be delivered intravenously in escalating doses of 1 x 10 6 MSC/kg, 3 x 10 6 MSC/kg, 6 x 10 6 MSC/kg, or 10 x 10 6 MSC/kg of body weight to a population of patients with idiopathic Parkinson's disease (iPD).
• Allogeneic bone marrow-derived MSCs (3 x 10 6 MSC/kg)
Bone marrow-derived allogeneic MSCs will be delivered intravenously in escalating doses of 1 x 10 6 MSC/kg, 3 x 10 6 MSC/kg, 6 x 10 6 MSC/kg, or 10 x 10 6 MSC/kg of body weight to a population of patients with idiopathic Parkinson's disease (iPD).
• Allogeneic bone marrow-derived MSCs (6 x 10 6 MSC/kg)
Bone marrow-derived allogeneic MSCs will be delivered intravenously in escalating doses of 1 x 10 6 MSC/kg, 3 x 10 6 MSC/kg, 6 x 10 6 MSC/kg, or 10 x 10 6 MSC/kg of body weight to a population of patients with idiopathic Parkinson's disease (iPD).
• Allogeneic bone marrow-derived MSCs (10 x 10 6 MSC/kg)
Bone marrow-derived allogeneic MSCs will be delivered intravenously in escalating doses of 1 x 10 6 MSC/kg, 3 x 10 6 MSC/kg, 6 x 10 6 MSC/kg, or 10 x 10 6 MSC/kg of body weight to a population of patients with idiopathic Parkinson's disease (iPD).

Locations

Country	Name	City	State
United States	The University of Texas Health Science Center at Houston	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
The University of Texas Health Science Center, Houston

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of allogeneic MSC therapy in patients with iPD as indicated by the presence of adverse events that are confirmed to be related to the therapy	Adverse events include renal failure, liver failure, and hemolytic anemia.	3 weeks after the first infusion
Primary	Safety of allogeneic MSC therapy in patients with iPD as indicated by the presence of adverse events that are confirmed to be related to the therapy	Adverse events include renal failure, liver failure, and hemolytic anemia.	12 weeks after the first infusion
Primary	Safety of allogeneic MSC therapy in patients with iPD as indicated by the presence of adverse events that are confirmed to be related to the therapy	Adverse events include renal failure, liver failure, and hemolytic anemia.	24 weeks after the first infusion
Primary	Safety of allogeneic MSC therapy in patients with iPD as indicated by the presence of adverse events that are confirmed to be related to the therapy	Adverse events include renal failure, liver failure, and hemolytic anemia.	52 weeks after the first infusion
Secondary	Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Total score	The UPDRS serves as a disability and impairment scale for progression follow-up and is divided into four sections.; Part I: evaluation of mentation, behavior, and mood (13 questions).; Part II: evaluation of activities of daily living including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food (13 questions).; Part III: motor examination (33 scores based on 18 questions with right, left or other body distributions scores); Part IV: motor complications (6 questions); All items have 5 response options with uniform anchors of: 0 = normal, 1 = slight (symptoms/signs with sufficiently low frequency or intensity to cause no impact on function), 2 = mild (symptoms/signs of frequency or intensity sufficient to cause a modest impact on function, 3 = moderate (symptoms/signs sufficiently frequent or intense to impact considerably, but not prevent function), 4 = severe (symptoms/signs that prevent function).	baseline, 3 weeks
Secondary	Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Total score	The UPDRS serves as a disability and impairment scale for progression follow-up and is divided into four sections.; Part I: evaluation of mentation, behavior, and mood (13 questions).; Part II: evaluation of activities of daily living including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food (13 questions).; Part III: motor examination (33 scores based on 18 questions with right, left or other body distributions scores); Part IV: motor complications (6 questions); All items have 5 response options with uniform anchors of: 0 = normal, 1 = slight (symptoms/signs with sufficiently low frequency or intensity to cause no impact on function), 2 = mild (symptoms/signs of frequency or intensity sufficient to cause a modest impact on function, 3 = moderate (symptoms/signs sufficiently frequent or intense to impact considerably, but not prevent function), 4 = severe (symptoms/signs that prevent function).	baseline, 12 weeks
Secondary	Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Total score	The UPDRS serves as a disability and impairment scale for progression follow-up and is divided into four sections.; Part I: evaluation of mentation, behavior, and mood (13 questions).; Part II: evaluation of activities of daily living including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food (13 questions).; Part III: motor examination (33 scores based on 18 questions with right, left or other body distributions scores); Part IV: motor complications (6 questions); All items have 5 response options with uniform anchors of: 0 = normal, 1 = slight (symptoms/signs with sufficiently low frequency or intensity to cause no impact on function), 2 = mild (symptoms/signs of frequency or intensity sufficient to cause a modest impact on function, 3 = moderate (symptoms/signs sufficiently frequent or intense to impact considerably, but not prevent function), 4 = severe (symptoms/signs that prevent function).	baseline, 24 weeks
Secondary	Change in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Total score	The UPDRS serves as a disability and impairment scale for progression follow-up and is divided into four sections.; Part I: evaluation of mentation, behavior, and mood (13 questions).; Part II: evaluation of activities of daily living including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food (13 questions).; Part III: motor examination (33 scores based on 18 questions with right, left or other body distributions scores); Part IV: motor complications (6 questions); All items have 5 response options with uniform anchors of: 0 = normal, 1 = slight (symptoms/signs with sufficiently low frequency or intensity to cause no impact on function), 2 = mild (symptoms/signs of frequency or intensity sufficient to cause a modest impact on function, 3 = moderate (symptoms/signs sufficiently frequent or intense to impact considerably, but not prevent function), 4 = severe (symptoms/signs that prevent function).	baseline, 52 weeks
Secondary	Change in motor function as assessed by the UPDRS Motor score	Parts III and IV of the UPDRS will be performed as described above.	baseline, 3 weeks
Secondary	Change in motor function as assessed by the UPDRS Motor score	Parts III and IV of the UPDRS will be performed as described above.	baseline, 12 weeks
Secondary	Change in motor function as assessed by the UPDRS Motor score	Parts III and IV of the UPDRS will be performed as described above.	baseline, 24 weeks
Secondary	Change in motor function as assessed by the UPDRS Motor score	Parts III and IV of the UPDRS will be performed as described above.	baseline, 52 weeks
Secondary	Change in motor function as assessed by Timed-Up-and-Go (TUG)	Time in seconds required to stand from a chair, walk 7meters, turn, walk back to the chair and sit down.	baseline, 3 weeks
Secondary	Change in motor function as assessed by Timed-Up-and-Go (TUG)	Time in seconds required to stand from a chair, walk 7meters, turn, walk back to the chair and sit down.	baseline, 12 weeks
Secondary	Change in motor function as assessed by Timed-Up-and-Go (TUG)	Time in seconds required to stand from a chair, walk 7meters, turn, walk back to the chair and sit down.	baseline, 24 weeks
Secondary	Change in motor function as assessed by Timed-Up-and-Go (TUG)	Time in seconds required to stand from a chair, walk 7meters, turn, walk back to the chair and sit down.	baseline, 52 weeks
Secondary	Change in disability as measured by the Modified Hoehn and Yahr Scale	The Modified Hoehn and Yahr Scale is a staging instrument that defines broad categories of motor function in Parkinson's disease, starting at Stage 0: no signs of disease to the highest stage 5: wheelchair bound or bedridden unless aided.	baseline, 3 weeks
Secondary	Change in disability as measured by the Modified Hoehn and Yahr Scale	The Modified Hoehn and Yahr Scale is a staging instrument that defines broad categories of motor function in Parkinson's disease, starting at Stage 0: no signs of disease to the highest stage 5: wheelchair bound or bedridden unless aided.	baseline, 12 weeks
Secondary	Change in disability as measured by the Modified Hoehn and Yahr Scale	The Modified Hoehn and Yahr Scale is a staging instrument that defines broad categories of motor function in Parkinson's disease, starting at Stage 0: no signs of disease to the highest stage 5: wheelchair bound or bedridden unless aided.	baseline, 24 weeks
Secondary	Change in disability as measured by the Modified Hoehn and Yahr Scale	The Modified Hoehn and Yahr Scale is a staging instrument that defines broad categories of motor function in Parkinson's disease, starting at Stage 0: no signs of disease to the highest stage 5: wheelchair bound or bedridden unless aided.	baseline, 52 weeks
Secondary	functional connectivity between substantia nigra and dorsal striatum as assessed by resting state functional magnetic resonance imaging (fMRI)	Diffusion tensor and T2 imaging with the resting state functional connectivity technique will be used.	baseline
Secondary	perfusion as assessed by arterial spin-labeled (ASL) perfusion MRI	Resting cerebral blood flow (CBF) will be measured using a pseudo-continuous arterial spin labeling (pCASL) MRI sequence with gradient-echo echo-planar imaging (EPI), which allows for a non-invasive quantification of CBF.	baseline
Secondary	structural connectivity as assessed by diffusion-weighted MRI for diffusion tensor image (DTI) analysis	A set of diffusion-weighted image volumes (32-directions, high angular resolution) will be collected using the gradient overplus option with one B0 (non-diffusion weighted) image volume acquired before the acquisition of one repetition of the diffusion-weighted scans. Diffusion tensor and associated computations will be performed. White matter microstructure will be examined, which represents the structural pathways linking specific cortical and subcortical regions. It will be determined whether there is increased fractional anisotropy and decreased mean diffusivity along white matter fibers that link regions exhibiting increased functional connectivity, such as substantia nigra and dorsal striatum.	baseline
Secondary	volume of subcortical structures as assessed by T1- and T2- weighted MRI with Fluid Attenuated Inversion Recovery	Anatomical imaging allows visualization of the brain structure at the level of about 1 cubic millimeter. These scans will be used to estimate the volume of subcortical structures (e.g., putamen, caudate nucleus).	baseline
Secondary	cortical thickness as assessed by T1- and T2- weighted MRI with Fluid Attenuated Inversion Recovery	Anatomical imaging allows visualization of the brain structure at the level of about 1 cubic millimeter. These scans will be used to measure cortical thickness (e.g., gray matter density).	baseline
Secondary	Change in gross brain structure as assessed by T1- and T2- weighted MRI with Fluid Attenuated Inversion Recovery	Anatomical imaging allows visualization of the brain structure at the level of about 1 cubic millimeter. These scans will be used to detect any gross structural changes or inflammation that appear during the course of treatment.	baseline
Secondary	Change in brain activity as assessed by task state fMRI	Whole-brain echo-planar imaging (EPI) runs sensitive to BOLD contrast will be acquired while participants do self-paced finger tapping using their left and right hands at separate points in time, and during the resting state after being instructed to remain still and fixate on a white crosshair displayed on a black background during the functional acquisition. Functional imaging will be done in the OFF medication state. It will be determined whether there is a reduction in the abnormally high activity pattern in motor cortex and an increase in putamen activity.	baseline
Secondary	Change in quality of life as assessed by the modified Schwab and England activities of daily living (ADL) score	The Schwab & England scale is a physician assessment of the subject's level of independence. The subject will be scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to what he/she did before Parkinson disease appeared. Scores range from 100% to 0% in increments of 10%, where 100% is completely independent and 0% is only vegetative functions.	baseline, 3 weeks
Secondary	Change in quality of life as assessed by the modified Schwab and England activities of daily living (ADL) score	The Schwab & England scale is a physician assessment of the subject's level of independence. The subject will be scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to what he/she did before Parkinson disease appeared. Scores range from 100% to 0% in increments of 10%, where 100% is completely independent and 0% is only vegetative functions.	baseline, 12 weeks
Secondary	Change in quality of life as assessed by the modified Schwab and England activities of daily living (ADL) score	The Schwab & England scale is a physician assessment of the subject's level of independence. The subject will be scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to what he/she did before Parkinson disease appeared. Scores range from 100% to 0% in increments of 10%, where 100% is completely independent and 0% is only vegetative functions.	baseline, 24 weeks
Secondary	Change in quality of life as assessed by the modified Schwab and England activities of daily living (ADL) score	The Schwab & England scale is a physician assessment of the subject's level of independence. The subject will be scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to what he/she did before Parkinson disease appeared. Scores range from 100% to 0% in increments of 10%, where 100% is completely independent and 0% is only vegetative functions.	baseline, 52 weeks
Secondary	Change in quality of life as assessed by the Parkinson's Disease Questionnaire (PDQ-39)	The PDQ-39 is a 39 questions Parkinson's Disease self-completed questionnaire that comprises 8 domains: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items). All items are assumed to impact QoL and must be answered to compute scores for each dimension. Questions are answered based on experiences from the preceding month using a 5-point ordinal scoring system: 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always. Each scores range from 0 = never have difficulty to 100 = always have difficulty.	baseline, 3 weeks
Secondary	Change in quality of life as assessed by the Parkinson's Disease Questionnaire (PDQ-39)	The PDQ-39 is a 39 questions Parkinson's Disease self-completed questionnaire that comprises 8 domains: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items). All items are assumed to impact QoL and must be answered to compute scores for each dimension. Questions are answered based on experiences from the preceding month using a 5-point ordinal scoring system: 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always. Each scores range from 0 = never have difficulty to 100 = always have difficulty.	baseline, 12 weeks
Secondary	Change in quality of life as assessed by the Parkinson's Disease Questionnaire (PDQ-39)	The PDQ-39 is a 39 questions Parkinson's Disease self-completed questionnaire that comprises 8 domains: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items). All items are assumed to impact QoL and must be answered to compute scores for each dimension. Questions are answered based on experiences from the preceding month using a 5-point ordinal scoring system: 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always. Each scores range from 0 = never have difficulty to 100 = always have difficulty.	baseline, 24 weeks
Secondary	Change in quality of life as assessed by the Parkinson's Disease Questionnaire (PDQ-39)	The PDQ-39 is a 39 questions Parkinson's Disease self-completed questionnaire that comprises 8 domains: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items). All items are assumed to impact QoL and must be answered to compute scores for each dimension. Questions are answered based on experiences from the preceding month using a 5-point ordinal scoring system: 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always. Each scores range from 0 = never have difficulty to 100 = always have difficulty.	baseline, 52 weeks
Secondary	Change in cognitive function as assessed by the Montreal Cognitive Assessment (MoCA)	The Montreal Cognitive Assessment is a rapid screening instrument for working memory, visual-spatial abilities, executive function, attention, concentration, language and orientation. The total score ranges from 0 to 30; a score of 26 or above is considered normal.	baseline, 52 weeks
Secondary	Change in immunologic response as assessed by plasma concentrations of cytokines	Investigators will assess cytokines associated with inflammation [interleukin-6 (IL-6), Interleukin-1 beta (IL-1ß), Tumor Necrosis Factor beta (TNFß)]; cell growth and differentiation [Brain-derived neurotrophic factor (BDNF), Granulocyte-macrophage colony-stimulating factor (GM-CSF)]; monocyte migration [Fractalkine, Eotaxin, monocyte chemotactic protein 1 (MCP-1), Macrophage Inflammatory Protein 1 beta (MIP-1ß)]; and adaptive immune response [interleukin 12 subunit beta (IL-12p40), interleukin 7 (IL-7), interleukin 9 (IL-9), interleukin 4 (IL-4)] will be measured.	baseline, 3 weeks
Secondary	Change in immunologic response as assessed by plasma concentrations of cytokines	Investigators will assess cytokines associated with inflammation [interleukin-6 (IL-6), Interleukin-1 beta (IL-1ß), Tumor Necrosis Factor beta (TNFß)]; cell growth and differentiation [Brain-derived neurotrophic factor (BDNF), Granulocyte-macrophage colony-stimulating factor (GM-CSF)]; monocyte migration [Fractalkine, Eotaxin, monocyte chemotactic protein 1 (MCP-1), Macrophage Inflammatory Protein 1 beta (MIP-1ß)]; and adaptive immune response [interleukin 12 subunit beta (IL-12p40), interleukin 7 (IL-7), interleukin 9 (IL-9), interleukin 4 (IL-4)] will be measured.	baseline, 12 weeks
Secondary	Change in immunologic response as assessed by plasma concentrations of cytokines	Investigators will assess cytokines associated with inflammation [interleukin-6 (IL-6), Interleukin-1 beta (IL-1ß), Tumor Necrosis Factor beta (TNFß)]; cell growth and differentiation [Brain-derived neurotrophic factor (BDNF), Granulocyte-macrophage colony-stimulating factor (GM-CSF)]; monocyte migration [Fractalkine, Eotaxin, monocyte chemotactic protein 1 (MCP-1), Macrophage Inflammatory Protein 1 beta (MIP-1ß)]; and adaptive immune response [interleukin 12 subunit beta (IL-12p40), interleukin 7 (IL-7), interleukin 9 (IL-9), interleukin 4 (IL-4)] will be measured.	baseline, 24 weeks
Secondary	Change in immunologic response as assessed by plasma concentrations of cytokines	Investigators will assess cytokines associated with inflammation [interleukin-6 (IL-6), Interleukin-1 beta (IL-1ß), Tumor Necrosis Factor beta (TNFß)]; cell growth and differentiation [Brain-derived neurotrophic factor (BDNF), Granulocyte-macrophage colony-stimulating factor (GM-CSF)]; monocyte migration [Fractalkine, Eotaxin, monocyte chemotactic protein 1 (MCP-1), Macrophage Inflammatory Protein 1 beta (MIP-1ß)]; and adaptive immune response [interleukin 12 subunit beta (IL-12p40), interleukin 7 (IL-7), interleukin 9 (IL-9), interleukin 4 (IL-4)] will be measured.	baseline, 52 weeks
Secondary	Change in suicidal ideation or behaviors as assessed by and Columbia Suicide Severity Rating Scale (CSSRS)	The CSSRS rating scale is a set of questions directed towards eliciting verbalization of suicidal feelings or actions	Screening, 3 weeks, 12 weeks, 24 weeks, 52 weeks