Adipose tissue-derived stromal vascular fraction for treating hands of patients with systemic sclerosis: a multicentre randomized trial Autologous AD-SVF versus placebo in systemic sclerosis
Aurélie Daumas
(1, 2)
,
Jérémy Magalon
(2, 3)
,
Elisabeth Jouve
(4)
,
Dominique Casanova
(5)
,
Cécile Philandrianos
(5)
,
Maxime Abellan Lopez
(5)
,
Stéphanie Mallet
(5)
,
Julie Veran
(3)
,
Isabelle Auquit-Auckbur
(6, 7)
,
Dominique Farge
(8, 9, 10)
,
Hervé Levesque
(11, 12)
,
Ygal Benhamou
(11, 12)
,
Laurent Arnaud
(3)
,
Laurent Giraudo
(3)
,
Chloé Dumoulin
(3)
,
Camille Giverne
(7, 6)
,
Olivier Boyer
(7, 6)
,
Alexandra Giuliani
(5)
,
Véronique Bourgarel
(5, 13)
,
Jean-Robert Harlé
(5)
,
Nicolas Schleinitz
(5)
,
Julie Brunet
(5)
,
Yves-Marie Pers
(14, 15)
,
Rosanna Ferreira
(14)
,
Audrey Cras
(8, 16)
,
David Bocara
(8)
,
Jérôme Larghero
(16, 8)
,
Joseph Château
(17)
,
Arnaud Hot
(18)
,
Françoise Dignat-George
(5)
,
Guy Magalon
(5)
,
Florence Sabatier
(5, 3)
,
Brigitte Granel
(3, 5)
1
LA CONCEPTION -
Hôpital de la Conception [CHU - APHM]
2 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
3 CIC - Centre d'Investigation Clinique [Hôpital de la Conception - APHM]
4 Hôpital Nord [CHU - APHM]
5 APHM - Assistance Publique - Hôpitaux de Marseille
6 CHU Rouen
7 PANTHER - Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices
8 AP-HP - Hopital Saint-Louis [AP-HP]
9 URP_3518 - Recherche clinique appliquée à l'hématologie
10 McGill University = Université McGill [Montréal, Canada]
11 Service de Médecine Interne [CHU Rouen]
12 EnVI - Endothélium, valvulopathies et insuffisance cardiaque
13 CRCM - Centre de Recherche en Cancérologie de Marseille
14 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
15 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
16 HIPI (UMR_S_976 / U976) - Immunologie humaine, physiopathologie & immunothérapie
17 Hôpital privé Jean Mermoz [Lyon]
18 Hôpital Edouard Herriot [CHU - HCL]
2 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
3 CIC - Centre d'Investigation Clinique [Hôpital de la Conception - APHM]
4 Hôpital Nord [CHU - APHM]
5 APHM - Assistance Publique - Hôpitaux de Marseille
6 CHU Rouen
7 PANTHER - Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices
8 AP-HP - Hopital Saint-Louis [AP-HP]
9 URP_3518 - Recherche clinique appliquée à l'hématologie
10 McGill University = Université McGill [Montréal, Canada]
11 Service de Médecine Interne [CHU Rouen]
12 EnVI - Endothélium, valvulopathies et insuffisance cardiaque
13 CRCM - Centre de Recherche en Cancérologie de Marseille
14 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
15 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
16 HIPI (UMR_S_976 / U976) - Immunologie humaine, physiopathologie & immunothérapie
17 Hôpital privé Jean Mermoz [Lyon]
18 Hôpital Edouard Herriot [CHU - HCL]
Aurélie Daumas
- Fonction : Auteur
- PersonId : 1035639
Dominique Farge
- Fonction : Auteur
- PersonId : 1021173
- ORCID : 0000-0002-4041-1352
Hervé Levesque
- Fonction : Auteur
- PersonId : 1066645
Ygal Benhamou
- Fonction : Auteur
- PersonId : 1052080
Laurent Arnaud
- Fonction : Auteur
- PersonId : 735667
- IdHAL : laurent-arnaud
- ORCID : 0000-0002-4432-4205
- IdRef : 026691019
Olivier Boyer
- Fonction : Auteur
- PersonId : 953124
Audrey Cras
- Fonction : Auteur
- PersonId : 770676
- ORCID : 0000-0002-6894-9584
- IdRef : 094131309
Jérôme Larghero
- Fonction : Auteur
- PersonId : 887236
- ORCID : 0000-0003-2086-7448
- IdRef : 06911613X
Françoise Dignat-George
- Fonction : Auteur
- PersonId : 172613
- IdHAL : francoise-dignat-george
- ORCID : 0000-0001-7006-4462
- IdRef : 061626430
Brigitte Granel
- Fonction : Auteur
- PersonId : 775933
- ORCID : 0000-0001-7995-8817
- IdRef : 112033881
Résumé
Objective: To assess the superiority of adipose tissue-derived stromal vascular fraction (AD-SVF) injection into the fingers vs placebo in reducing hand disability in systemic sclerosis (SSc) patients.
Methods: We performed a double-blind, multicentre, phase II trial from October 2015 to January 2018 in France. SSc patients with a Cochin Hand Function Scale (CHFS) ≥20/90 were randomized 1:1 to receive injection of AD-SVF or placebo. AD-SVF was obtained using the automated processing Celution®800/CRS system. The placebo was lactated Ringer's solution. The primary efficacy end point was the change of the CHFS score from baseline to 3 months. Secondary efficacy endpoints included the CHFS score at 6 months, hands function, vasculopathy, hands pain, skin fibrosis, sensitivity of the finger' pulps, Scleroderma Health Assessment Questionnaire, patients and physician satisfaction and the safety.
Results: 40 patients were randomized. The AD-SVF and placebo groups were comparable for age, sex ratio, disease duration, skin fibrosis of the hands and main cause of hand disability. After 3 month-follow-up, hand function significantly improved in both groups with no between-group difference of CHFS (mean change of -9.2 ± 12.2 in the AD-SVF group vs -7.6 ± 13.2 in the placebo group). At 6 months, hand function improved in both groups.
Conclusion: This study showed an improvement of hand function in both groups other time, with no superiority of the AD-SVF. Considering the limits of this trial, studies on a larger population of patients with homogeneous phenotype and hand handicap, should be encouraged to accurately assess the benefit of AD-SVF therapy.
Trial registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02558543. Registered on September 24, 2015.