PDF: AMASCIS
(2022)Objective
To evaluate the long-term safety and explore the efficacy of intravenous allogeneic adipose-derived mesenchymal stem cells (AD-MSCs) in patients with acute ischemic stroke.
Study Summary
• The primary outcome was met: intravenous AD-MSC treatment was found to be safe over a 24-month follow-up, with no treatment-related serious adverse events or tumor development.
• The trial was significantly underpowered to assess efficacy, and no significant differences in functional outcomes (modified Rankin Scale score) were found between the groups.
Intervention
A single intravenous dose of allogeneic adipose-derived mesenchymal stem cells (AD-MSCs) at a dose of 1 million cells/kg or a placebo infusion, administered within 2 weeks of moderate-to-severe ischemic stroke onset. Patients were followed for 24 months.
Study Design
Arms: AD-MSCs (adipose-derived mesenchymal stem cells) vs Placebo
Outcome
• For efficacy, there were no significant differences in modified Rankin Scale (mRS) scores between the groups at 24 months. There was a non-significant trend toward lower NIHSS scores in the AD-MSC group.
Bottom Line
Intravenous treatment with allogeneic AD-MSCs administered within the first two weeks of ischemic stroke was found to be safe at 24 months of follow-up. The trial was significantly underpowered to detect efficacy, and no significant differences in functional outcomes were observed between the treatment groups.
Major Points
- AMASCIS was a phase IIa, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial.
- The study planned to enroll 20 patients aged 60 years or older with moderate to severe stroke (NIHSS 8-20), but recruitment stopped after 19 patients were enrolled.
- Due to exclusions after randomization (eg, technical issues, developing exclusion criteria), the final treated study sample consisted of only 13 patients (4 receiving AD-MSCs and 9 receiving placebo).
- The primary outcome was safety over 24 months. The treatment was found to be safe, with no injection-related adverse events or tumor development. The total number of adverse events and complications was similar between groups.
- The secondary efficacy outcome, measured by the modified Rankin Scale (mRS), showed no significant differences between the AD-MSC and placebo groups at any follow-up point up to 24 months.
- At 24 months, patients in the AD-MSC group showed a non-significantly lower median NIHSS score compared to the placebo group (3 vs 7).
Study Design
- Study Type
- Phase IIa, pilot, single-center, prospective, randomized, double-blind, placebo-controlled clinical trial
- Randomization
- Yes
- Blinding
- Double-blind
- Sample Size
- 13
- Follow-up
- 24 months
- Centers
- 1
- Countries
- Spain
Primary Outcome
Definition: Safety, assessed by evaluating adverse events (AEs), serious AEs, neurologic and systemic complications, and tumor development over 24 months.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Nine non-treatment-related serious AEs occurred. One patient died due to sepsis. | Two non-treatment-related serious AEs occurred. No injection-related AEs or tumor development were registered. | - |
Limitations & Criticisms
- The primary limitation is the very small final sample size (n=13, with only 4 in the treatment group), which severely underpowered the study for any efficacy analysis.
- A high number of enrolled patients (6 out of 19) did not receive the study treatment for various reasons, further reducing the sample size and potentially introducing selection bias.
- There was a statistically significant difference in the time from stroke onset to treatment administration between the groups (median 13 days for AD-MSC vs. 12 days for placebo, P=0.028).
Citation
Cell Transplantation. 2022;31:1-11