Stem Cell Therapy for Bipolar Depression

Overseen By Dana Razouq

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: The University of Texas Health Science Center, Houston

Must be taking: Mood stabilizers

Must not be taking: Anticonvulsants

Disqualifiers: Brain injury, Renal disease, Hepatic disease, Cancer, others

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses special cells from donated bone marrow to treat patients with bipolar depression who haven't responded to standard treatments. The cells may help by reducing inflammation and promoting brain healing. This approach has shown promise in preventing depression and anxiety in animal studies.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the trial is for treatment-resistant bipolar depression, it might be assumed that participants are already on mood stabilizers or antidepressants.

What data supports the effectiveness of the treatment Allogeneic Bone Marrow Derived Multipotent Mesenchymal Stromal Cells (MSCs) for bipolar depression?

Research suggests that lithium, a common treatment for bipolar disorder, can enhance the growth and transformation of mesenchymal stem cells (MSCs) into neural cells, which may improve their effectiveness in treating central nervous system disorders. This indicates potential benefits of MSCs in managing conditions like bipolar depression. ^{1 2 3 4 5}

Is stem cell therapy safe for humans?

Research on mesenchymal stem cells (MSCs) suggests they have been used in various studies, including for depression and traumatic brain injury, without specific safety concerns reported. However, detailed safety data for humans is limited, and more research is needed to confirm their safety in clinical settings. ^{2 3 6 7 8}

How is the stem cell treatment for bipolar depression different from other treatments?

This stem cell treatment is unique because it uses mesenchymal stem cells (MSCs) to promote neurogenesis (the growth of new brain cells), which may help address hippocampal atrophy linked to bipolar disorder. Unlike traditional medications like lithium, which may not work for everyone, this approach aims to stimulate brain repair and growth directly. ^{1 2 5 9 10}

Research Team

Jair C Soares, MD, PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

This trial is for adults aged 18-65 with treatment-resistant bipolar depression, confirmed by specific interviews and hospital records. Participants must have a CRP level over 5 mg/L, not be pregnant or breastfeeding, use contraception if applicable, and be fluent in English for testing purposes. They should have had less than a 50% reduction in depression symptoms after previous treatments.

Inclusion Criteria

I have been diagnosed with Bipolar I or II disorder.

I have been diagnosed with a severe depressive episode.

Patient sufficiently fluent in English language to ensure valid responses to psychometric testing (needed for validated neurocognitive outcomes testing)

Exclusion Criteria

Inability to comply with study protocol

You have a medical condition that is not well controlled, which may affect your ability to participate in the trial. You also have a condition that may affect your neuropsychological assessment or have a history of substance abuse.

I am stable and do not have severe fluctuations in my blood pressure or heart rate.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive a single dose of MSCs or placebo and continue with treatment as usual for 8 weeks

8 weeks

1 visit (in-person) for infusion

Follow-up

Participants are monitored for safety and effectiveness, including neurocognitive and clinical assessments at week 26

18 weeks

1 visit (in-person) at week 26

Treatment Details

Interventions

• Allogeneic Bone Marrow Derived Multipotent Mesenchymal Stromal Cells (MSCs)
• Placebo

Trial Overview The study tests the effectiveness of Allogeneic Bone Marrow Derived Mesenchymal Stromal Cells (MSCs) against a placebo in treating bipolar depression that hasn't improved with standard treatments. The MSCs are derived from bone marrow to see if they can help alleviate depressive symptoms.

Participant Groups

Group I: Allogeneic Bone Marrow Derived Multipotent Mesenchymal Stromal Experimental Treatment 1 Intervention

Allogeneic Bone Marrow Derived Multipotent Mesenchymal Stromal Cells (MSCs) isolated from hematogenous bone marrow

Group II: Placebo Placebo Group 1 Intervention

Placebo for Allogeneic Bone Marrow Derived Multipotent Mesenchymal Stromal Cells (MSCs)

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Findings from Research

Hippocampal neurons derived from induced pluripotent stem cells (iPSCs) of bipolar disorder (BD) patients exhibit hyperexcitability, which is confirmed across different patient cohorts, indicating a consistent cellular characteristic of the disorder.

The study identifies two sub-populations of BD neurons based on lithium responsiveness, with lithium treatment effectively reducing hyperexcitability in lithium-responsive patients but not in non-responsive patients, highlighting the potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurons derived from patients with bipolar disorder divide into intrinsically different sub-populations of neurons, predicting the patients' responsiveness to lithium. Stern, S., Santos, R., Marchetto, MC., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Lithium enhanced cell proliferation and differentiation of mesenchymal stem cells to neural cells in rat spinal cord. [2018]

3. England pubmed.ncbi.nlm.nih.gov

The effect of long-term lithium treatment of bipolar disorder on stem cells circulating in peripheral blood. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Neurons derived from patients with bipolar disorder divide into intrinsically different sub-populations of neurons, predicting the patients' responsiveness to lithium. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Generation of four iPSC lines from a family harboring a 1p36-35 haplotype linked with bipolar disorder and recurrent depressive disorder: Three-generation patients and a healthy sibling. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Use of human mesenchymal stem cell treatment to prevent anhedonia in a rat model of traumatic brain injury. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Mood stabilizing drugs expand the neural stem cell pool in the adult brain through activation of notch signaling. [2008]

8. England pubmed.ncbi.nlm.nih.gov

Cell encapsulation enhances antidepressant effect of the mesenchymal stem cells and counteracts depressive-like behavior of treatment-resistant depressed rats. [2021]

9. Brazil pubmed.ncbi.nlm.nih.gov

Cell therapy in the treatment of bipolar mania in an animal model: a proof of concept study. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Characterization of bipolar disorder patient-specific induced pluripotent stem cells from a family reveals neurodevelopmental and mRNA expression abnormalities. [2018]