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Clinical Trial
. 2013 Jun 10:11:143.
doi: 10.1186/1479-5876-11-143.

A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia

Pawan K Gupta  1 , Anoop Chullikana, Rajiv Parakh, Sanjay Desai, Anjan Das, Sanjay Gottipamula, Sagar Krishnamurthy, Naveen Anthony, Arun Pherwani, Anish S Majumdar
Affiliations
Clinical Trial

A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia

Pawan K Gupta et al. J Transl Med. .

Abstract

Background: Peripheral vascular disease of the lower extremities comprises a clinical spectrum that extends from no symptoms to presentation with critical limb ischemia (CLI). Bone marrow derived Mesenchymal Stem Cells (BM- MSCs) may ameliorate the consequences of CLI due to their combinatorial potential for inducing angiogenesis and immunomodulatory environment in situ. The primary objective was to determine the safety of BM- MSCs in patients with CLI.

Methods: Prospective, double blind randomized placebo controlled multi-center study was conducted in patients with established CLI as per Rutherford classification in category II-4, III-5, or III-6 with infra-inguinal arterial occlusive disease and were not suitable for or had failed revascularization treatment. The primary end point was incidence of treatment - related adverse events (AE). Exploratory efficacy end points were improvement in rest pain, increase in Ankle Brachial Pressure Index (ABPI), ankle pressure, healing of ulcers, and amputation rates. Twenty patients (BM-MSC: Placebo = 1:1) were administered with allogeneic BM-MSCs at a dose of 2 million cells/kg or placebo (PlasmaLyte A) at the gastrocnemius muscle of the ischemic limb.

Results: Improvement was observed in the rest pain scores in both the arms. Significant increase in ABPI and ankle pressure was seen in BM-MSC arm compared to the placebo group. Incidence of AEs in the BM-MSC arm was 13 vs. 45 in the placebo arm where as serious adverse events (SAE) were similar in both the arms (5 in BM-MSC and 4 in the placebo group). SAEs resulted in death, infected gangrene, amputations in these patients. It was observed that the SAEs were related to disease progression and not related to stem cells.

Conclusion: BM-MSCs are safe when injected IM at a dose of 2 million cells/kg body weight. Few efficacy parameters such as ABPI and ankle pressure showed positive trend warranting further studies.

Trial registration: NIH website (http://www.clinicaltrials.gov/ct2/show/NCT00883870).

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Figures

Figure 1
Figure 1
Total patients screened, allocated in each arm, followed up and analyzed in the trial. Diagram as per the Consolidated Standards of Reporting Trials (CONSORT) flow chart.
Figure 2
Figure 2
Immunological profile of patients in cell and placebo arm.
Figure 3
Figure 3
Efficacy parameters: Results of ABPI & Ankle pressure are shown as mean ± SD and corresponding p values. V1: screening; V4: 1 month; V5: 3 month; V6: 6 month follow – up.
See this image and copyright information in PMC

Comment in

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