Allogeneic Human Mesenchymal Stem Cells (hMSCs) Infusion in Patients With Treatment Resistant Depression (ANU)

A Phase I, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Potential Efficacy of Allogeneic Human Mesenchymal Stem Cell Infusion Versus Placebo in Patients With Treatment Resistant Depression.

This study is intended to evaluate the safety and potential efficacy of Allogeneic Human Mesenchymal Stem Cell Infusion versus placebo in patients with Treatment Resistant Depression.

Study Overview

• Status: Terminated
• Conditions: Treatment Resistant Depression
• Intervention / Treatment: Drug: Allo-hMSCs; Drug: Placebo

Detailed Description

This is a phase I study, with eight subjects in the pilot phase and eighty (80) subjects fulfilling all inclusion/exclusion criteria's will be randomly assigned to receive allogeneic Human Mesenchymal Stem Cell (hMSCs) or placebo in a 1:1 blinded fashion.

The 8 subjects in the pilot phase will receive a single infusion of 100 million hMSCs.

40 patients will receive a single administration of allogeneic hMSCs and another 40 patients will receive a single administration of Placebo in a 1:1 blinded fashion.

Following infusion, patients will be followed at 2, 4, 6, 8, 10 and 12 week's post-infusion to complete all safety and efficacy assessments. During these 12 weeks starting after the week 2 visit subjects will have a phone call in-between their visits. Patients will additionally be followed for up to 12 months post-infusion.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provide written informed consent.
2. Subjects age equal or greater than 18 and equal or less than 75 years at the time of signing the Informed Consent Form.
3. Diagnosis of Treatment resistant depression (Failed at least two adequate trials of antidepressant monotherapy or antidepressant augmentation with an antipsychotic or lithium during the current episode)
4. Patients who are receiving a third or more treatment will only be entered if they have not responded to the current treatment.
5. Experiencing a current Major Depressive Episode (fulfilling Structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders (DSM V) criteria per Structured Clinical Interview for DSM (SCID) for categorical diagnosis, and the Hamilton Depression Rating Scale for Depression (HAM-D))
6. Hamilton Depression Rating Scale 21-item score greater than 18
7. Adequacy of previous failed antidepressant trials will be defined using standard criteria by Massachusetts General Hospital (MGH) of patients with a score greater than or equal to 2.5
8. Increased inflammation ([Serum CRP] greater than 3.0 mg/L)

Exclusion Criteria:

In order to participate in this study, a patient Must Not:

1. Women who are pregnant, nursing, or of childbearing potential, while not practicing effective contraceptive methods. (Female subjects of childbearing potential must undergo a serum or urine pregnancy test at screening and within 36 hours prior to infusion.)
2. Inability to perform any of the assessments required.
3. Have clinically significant abnormal screening laboratory values, including but not limited to: hemoglobin <8 g/dl, white blood cell count <3000/mm3, platelets<80,000/mm3, INR > 1.5 not due to a reversible cause (i.e. Coumadin), aspartate transaminase, alanine transaminase, or alkaline phosphatase > 3 times upper limit of normal, total bilirubin > 1.8 mg/dl (unless due to a benign cause).
4. Active medical condition that could cause or exacerbate depressive symptoms (e.g., hypothyroidism, anemia)
5. Serious comorbid illness or any other condition (Such as bipolar, schizophrenia or schizoaffective disorder) that, in the opinion of the investigator, may compromise the safety or compliance of the subject or preclude successful completion of the study.
6. Have acute suicidality
7. Prior history of a suicide attempt, within the past year.
8. Active psychotic disorder, eating disorder, or substance use disorder within 6 months of enrollment
9. Treatment with any medication that, in the opinion of the Investigator, may compromise the safety of the subject or affect the validity of the data or the study endpoints.
10. First major depressive episode after 50 years of age.
11. Have known allergies to penicillin or streptomycin.
12. Have hypersensitivity to dimethyl sulfoxide (DMSO).
13. Have a clinical history of malignancy within 5 years (i.e., subjects with prior malignancy must be disease free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma.
14. Have a non-pulmonary condition that limits lifespan to < 1 year.
15. Have a history of drug or alcohol abuse within the past 24 months.
16. Be serum positive for HIV, hepatitis BsAg or Viremic hepatitis C.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Allogeneic hMSCs; Forty (40) subjects will be treated with a single administration of allogeneic Human Mesenchymal Stem Cell (hMSCs): 100 x 10^6 (100 million) allo-hMSCs of cells delivered via a single peripheral intravenous infusion.	Drug: Allo-hMSCs; a single administration of allogeneic Human Mesenchymal Stem Cell (hMSCs): 100 x 10^6 (100 million) allo-hMSCs of cells; Other Names: Stem Cells; Allogeneic Human Mesenchymal Stem Cells
Placebo Comparator: Placebo; Forty (40) subjects will be treated with a placebo administration consisting of 1% human albumin serum in Plasma-Lyte A delivered via a single peripheral intravenous infusion.	Drug: Placebo; a placebo administration consisting of 1% human albumin serum in Plasma-Lyte A
Experimental: Pilot - Allogeneic hMSCs; Eight (8) subjects will be treated with a single administration of allogeneic Human Mesenchymal Stem Cell (hMSCs): 100 x 10^6 (100 million) allo-hMSCs of cells delivered via a single peripheral intravenous infusion.	Drug: Allo-hMSCs; a single administration of allogeneic Human Mesenchymal Stem Cell (hMSCs): 100 x 10^6 (100 million) allo-hMSCs of cells; Other Names: Stem Cells; Allogeneic Human Mesenchymal Stem Cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of any treatment-emergent serious adverse events (TE-SAEs)	defined as a composite of acute suicidality, and hospitalization for suicide attempts.	One month post infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of Inflammation	Reduction of Inflammation: Change in serum concentrations of high sensitivity C-Reactive Protein (hs-CRP)	Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reductions in serum concentrations	Reductions in serum concentrations of other inflammatory markers;	Week 12
Reduction in Depressive Symptoms	Reduction in Depressive Symptoms due to change in Montgomery-Asberg Depression Rating Scale (MADRS)	Week 12
Reduction in Anhedonia	Reduction in Anhedonia due to change in the Snaith Hamilton Pleasure Scale	Week 12
Improvements in Cognition	Improvements in Cognition as a result of changes in Brief Assessment of Cognition for Affective Disorders (BAC-A), Performance Based Skills Assessment (UPSA-B), and Specific Level of Functioning (SLOF) scores	Week 12
Improvements in Functional Capacity	Improvements in Functional Capacity as a result of changes in Brief Assessment of Cognition for Affective Disorders (BAC-A), Performance Based Skills Assessment (UPSA-B), and Specific Level of Functioning (SLOF) scores	Week 12
Improvements in everyday functioning	Improvements in everyday functioning as a result of changes in Brief Assessment of Cognition for Affective Disorders (BAC-A), Performance Based Skills Assessment (UPSA-B), and Specific Level of Functioning (SLOF) scores	Week 12
Mediating effects of child abuse and neglect.	Mediating effects of child abuse and neglect.	week 12

Collaborators and Investigators

• Sponsor: Joshua M Hare
• Investigators: Study Director: Joshua M Hare, MD, ISCI / University of Miami Miller School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2017
• Primary Completion (Actual): March 26, 2019
• Study Completion (Actual): March 26, 2019

Study Registration Dates

• First Submitted: February 1, 2016
• First Submitted That Met QC Criteria: February 3, 2016
• First Posted (Estimate): February 5, 2016

Study Record Updates

• Last Update Posted (Actual): April 1, 2019
• Last Update Submitted That Met QC Criteria: March 28, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: 20140917

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No