title: First-in-man mesenchymal stem cells for radiation-induced xerostomia (MESRIX): study protocol for a randomized controlled trial.
abstract: Salivary gland hypofunction and xerostomia are major complications following radiotherapy for head and neck cancer and may lead to debilitating oral disorders and impaired quality of life. Currently, only symptomatic treatment is available. However, mesenchymal stem cell (MSC) therapy has shown promising results in preclinical studies. Objectives are to assess safety and efficacy in a first-in-man trial on adipose-derived MSC therapy (ASC) for radiation-induced xerostomia.
  
  
  
  This is a single-center, phase I/II, randomized, placebo-controlled, double-blinded clinical trial. A total of 30 patients are randomized in a 1:1 ratio to receive ultrasound-guided, administered ASC or placebo to the submandibular glands. The primary outcome is change in unstimulated whole salivary flow rate. The secondary outcomes are safety, efficacy, change in quality of life, qualitative and quantitative measurements of saliva, as well as submandibular gland size, vascularization, fibrosis, and secretory tissue evaluation based on contrast-induced magnetic resonance imaging (MRI) and core-needle samples. The assessments are performed at baseline (1 month prior to treatment) and 1 and 4 months following investigational intervention.
  
  
  
  The trial is the first attempt to evaluate the safety and efficacy of adipose-derived MSCs (ASCs) in patients with radiation-induced xerostomia. The results may provide evidence for the effectiveness of ASC in patients with salivary gland hypofunction and xerostomia and deliver valuable information for the design of subsequent trials.
  
  
  
  EudraCT, Identifier: 2014-004349-29. Registered on 1 April 2015. ClinicalTrials.gov, Identifier: NCT02513238 . First received on 2 July 2015. The trial is prospectively registered.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Section 2071, Blegdamsvej 9, 2100, Copenhagen, Denmark. c.gronhoj@gmail.com.
authors.forename: Christian
authors.identifier: 0000-0002-4524-8291
authors.initials: C
authors.lastname: Grønhøj
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Section 2071, Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: David H
authors.initials: DH
authors.lastname: Jensen
authors.affiliation: Department of Plastic Surgery, Breast Surgery and Burns, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Peter V
authors.initials: PV
authors.lastname: Glovinski
authors.affiliation: Department of Dentistry and Oral Health, Vennelyst Boulevard 9, DK-8000, Aarhus C, Denmark.|Department of Oral Medicine, Department of Odontology, Faculty Of Health and Medical Sciences, University of Copenhagen, Nørre Allé 20, DK-2200, Copenhagen N, Denmark.
authors.forename: Siri Beier
authors.initials: SB
authors.lastname: Jensen
authors.affiliation: Department of Oral Medicine, Department of Odontology, Faculty Of Health and Medical Sciences, University of Copenhagen, Nørre Allé 20, DK-2200, Copenhagen N, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Bardow
authors.affiliation: Cell Therapy Facility, The Blood Bank, Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Roberto S
authors.initials: RS
authors.lastname: Oliveri
authors.affiliation: Department of Oncology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Lena
authors.initials: L
authors.lastname: Specht
authors.affiliation: Department of Radiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Thomsen
authors.affiliation: Department of Computer Science, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen, Denmark.
authors.forename: Sune
authors.initials: S
authors.lastname: Darkner
authors.affiliation: Department of Pathology, Rigshospitalet, University of Copenhagen, Section 2071, Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Katalin
authors.initials: K
authors.lastname: Kiss
authors.affiliation: Cell Therapy Facility, The Blood Bank, Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Fischer-Nielsen
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Section 2071, Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: von Buchwald
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D062005:Biopsy, Large-Core Needle; D002985:Clinical Protocols; D003718:Denmark; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D009959:Oropharyngeal Neoplasms / Q000532:radiotherapy*; D011446:Prospective Studies; D011832:Radiation Injuries / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology / Q000601:surgery*; D020127:Recovery of Function; D012107:Research Design; D012472:Salivation; D013363:Submandibular Gland / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional; D014987:Xerostomia / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology / Q000601:surgery*
keywords: Mesenchymal stem cells; Xerostomia