The aim of this study was to evaluate the efficacy of intrasphincteric injections of autologous myoblasts (AMs) in fecal incontinence (FI) in a controlled study.
Summary of Background Data:
Adult stem cell therapy is expected to definitively cure FI by regenerating damaged sphincter. Preclinical data and results of open-label trials suggest that myoblast therapy may represent a noninvasive treatment option.
We conducted a phase 2 randomized, double-blind, placebo-controlled study of intrasphincteric injections of AM in 24 patients. The study compared outcome after AM (n = 12) or placebo (n = 12) injection using Cleveland Clinic Incontinence (CCI), score at 6 and 12 months. Patients in the placebo group were eligible to receive frozen AM after 1 year.
At 6 months, the median CCI score significantly decreased from baseline in both the AM (9 vs 15, P = 0.02) and placebo (10 vs 15, P = 0.01) groups. Hence, no significant difference was found between the 2 groups (primary endpoint) at 6 months. At 12 months, the median CCI score continued to ameliorate in the AM group (6.5 vs 15, P = 0.006), while effect was lost in the placebo group (14 vs 15, P = 0.35). Consequently, there was a higher response rate at 12 months in the treated than the placebo arm (58% vs 8%, P = 0.03). After delayed frozen AM injection in the placebo group, the response rate was 60% (6/10) at 12 months.
Intrasphincteric AM injections in FI patients have shown tolerance, safety, and clinical benefit at 12 months despite a transient placebo effect at 6 months.
Reprints: Professor Francis Michot, MD, PhD, Department of Digestive Surgery, Hôpital Charles Nicolle, 1 rue de Germont, F-76000 Rouen, France. E-mail: firstname.lastname@example.org.
OB and FM designed the original study. AB, JD, and SLC performed myoblast production under the supervision of OB, CG, and JM. SJ was responsible for quality control. PC organized and interpreted karyotypic analyses. DB organized the conservation of frozen myoblasts. FM performed implantation and coordinated patient follow-up. JJT and VB performed some delayed AM injections. AML supervised electrophysiological analyses. EK performed anal ultrasound analyses. JB designed the statistical plan and coordinated randomization. EH and JB performed statistical analyses. OB and VB wrote the initial version of the manuscript, which was edited by JB and FM. All authors contributed to the conception of the work and considered, revised, and approved the final version for submission.
This study was supported by a grant from the Programme Hospitalier de Recherche Clinique from the French Ministry of Health and, for a limited part, by Celogos (Paris, France). The work was completely independent. The Ministry of Health and Celogos had no role in the study design, or in the collection, analysis or interpretation of the data.
AB was the recipient of a PhD fellowship funded in part by Celogos. The other authors report no conflicts of interest.
Study Group of Myoblast Therapy for Fecal Incontinence: Patrice Valleur, Luc Sensebé, Rémi Morello, Guillaume Gourcerol, Céline Savoye-Collet, Géraldine Joly-Helas, Christelle Doucet, André Ulmann, Jean-Michel Flaman, Angélique Aublet, Lauriane Vittecoq, Chloé Modzelewski, Delphine Picoche, Noelle Frebourg, Sophie Boyer-Mariotte, Ludovic Lemée, Michèle Nouvellon, Christine Chefson, Lise Gourichon, Arnaud Roucheux, Fabienne Jouen, Julie Lamulle, Laetitia Demoulins, Ingrid Dutot, Sophie Ruault, Fabrice Duparc.
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