Adjunctive Allogeneic Mesenchymal Stem Cells for Treatment-resistant Bipolar Depression
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Treatment-resistant Bipolar Depression
- Sponsor
- The University of Texas Health Science Center, Houston
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Change in depression as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS)
- Status
- Recruiting
- Last Updated
- 10 months ago
Overview
Brief Summary
The overall objective of the investigators is to assess the therapeutic efficacy and tolerability of Allogeneic Bone Marrow Derived Multipotent Mesenchymal Stromal Cells (MSCs) isolated from hematogenous bone marrow for treatment of treatment-resistant bipolar depression patient (TRBD).
Detailed Description
This clinical trial is a randomized, double-blind, placebo-controlled study aiming to study the efficacy and side effects of MSCs adjunctive to TAU compared to a normal saline solution in patients with TRBD. Relevant patients with bipolar depression will be addressed in order to establish whether they are willing to be screened for the study. The patients must be assigned a patient number and sign the consent form after receiving oral and written information about the study prior to undergoing any study procedures. MSCs will be infused as a single dose up to one week after the inclusion of the patient. The treatment trial lasts eight weeks. Of note, the investigators will assess patients also at week 26 with a neurocognitive and clinical battery. It will not be allowed changes in psychiatric medication during this period. If a patient or the treating clinician decides that the patient could receive better treatment outside of the study, the patient may leave the study at all times, as specified in the informed consent. Patients were not allowed to take nonsteroidal or steroidal anti-inflammatory medications during the study. Medications for hypertension, diabetes, hypothyroidism, allergies, infections, or other medical conditions were allowed as dictated by the patients' treating physicians. The investigators defined refractory bipolar depression as depression that failed to respond to two trials (during lifetime) with antidepressants and/or mood stabilizer with proven efficacy in bipolar depression (lithium, lamotrigine, quetiapine, lurasidone, olanzapine) in adequate doses for at least 6 weeks or until cessation of treatment due to side effects (Schoeyen et al., 2015). After the initial injection, patients will continue maintenance treatment with their current psychiatrist. During this time, they will not receive additional injections but will receive treatment as usual per their clinician's choice. Patients will remain on stable psychiatric medications during this period. If patients need to change medications, they will be removed from the study protocol.
Investigators
Jair Soares
Professor
The University of Texas Health Science Center, Houston
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Placebo
Placebo for Allogeneic Bone Marrow Derived Multipotent Mesenchymal Stromal Cells (MSCs)
Intervention: Placebo
Outcomes
Primary Outcomes
Change in depression as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS)
Time Frame: baseline, week 8, week 26
The Montgomery-Åsberg Depression Rating Scale (MADRS) is a short and reliable scale devised to be sensitive to change. Patients are rated on ten items, each of which has value ranges from 0 (the least pathology) to 6 (the most sever pathology). Sum scores range from 0 to 60, with a scoring of 20 indicating moderate and 30 severe depression. The scale is sensitive to change and covers many, but not all, symptom domains in depression.
Secondary Outcomes
- Change in Clinical Global Impression Scale for Bipolar illness (CGI-BP), severity overall subscale(baseline, week 26)
- Change in Overall functioning in living as assessed by the Global Assessment of Functioning (GAF)(baseline, week 26)
- Number of participants with a change in brain activity between baseline and week 26 as assessed by Magnetic Resonance Imaging (MRI)(baseline, week 26)
- Number of participants who withdrawal due to Adverse Events (AEs)(week 26)
- Change in Clinical Global Impression Scale for Bipolar illness (CGI-BP), severity of mania subscale(baseline, week 26)
- Change in neurocognition as assessed by the California Verbal Learning Test(baseline, week 26)
- Change in problem-solving ability as assessed by the Wisconsin Card Sorting Test (WCST)(baseline, week 26)
- Number of participants with inflammatory markers as assessed by multiplex biomarker analysis(week 26)
- Change in brain-derived neurotrophic factor (BDNF) level as assessed by enzyme-linked immunosorbent assay (ELISA)(baseline, week 26)
- Change in C-reactive protein (CRP) level as assessed by enzyme-linked immunosorbent assay (ELISA)(baseline, week 26)
- Change in Clinical Global Impression Scale for Bipolar illness (CGI-BP), severity of depression subscale(baseline, week 26)
- Number of participants with suicidal ideation based on clinical assessment(week 26)
- Number of participants with treatment emergent mania or hypomania as assessed by the Young Mania Rating Scale (YMRS) and clinical assessment(week 26)
- Change in Functional impairment as assessed by the Functioning Assessment Short Test (FAST)(baseline, week 26)