PMID- 37658468
OWN - NLM
STAT- MEDLINE
DCOM- 20230904
LR  - 20231121
IS  - 1745-6215 (Electronic)
IS  - 1745-6215 (Linking)
VI  - 24
IP  - 1
DP  - 2023 Sep 1
TI  - Effectiveness and safety of mesenchymal stem/stromal cell for radiation-induced 
      hyposalivation and xerostomia in previous head and neck cancer patients 
      (MESRIX-III): a study protocol for a single-centre, double-blinded, randomised, 
      placebo-controlled, phase II study.
PG  - 567
LID - 10.1186/s13063-023-07594-5 [doi]
LID - 567
AB  - BACKGROUND: A predominant side effect of radiotherapy for head and neck cancer is 
      salivary gland hypofunction and xerostomia leading to debilitating oral disorders 
      and impaired quality of life (QoL). Intraglandular mesenchymal stem cell therapy 
      has shown promising results as a treatment for xerostomia. METHODS: This is a 
      randomised, double-blinded, placebo-controlled, parallel-group, prospective, 
      single-centre trial investigating the safety, tolerability, and effectiveness of 
      allogeneic stem cells as a treatment for radiation-induced hyposalivation and 
      xerostomia for previous head and neck cancer patients. We will include a total of 
      120 patients who previously have been treated with radiotherapy for a head and 
      neck cancer in Denmark. Participants will be randomly assigned using block 
      randomisation to one of two parallel groups in a 1:1 ratio to receive 
      ultrasound-guided injection of allogeneic adipose-derived mesenchymal stem cell 
      (ASC) (n = 60) or placebo (n = 60) into the submandibular glands. Placebo will 
      consist of CryoStor10 (BiolifeSolutions), the freeze media for ASCs containing 
      10% dimethyl sulfoxide (DMSO). The primary endpoint is change in unstimulated 
      whole saliva flow rate. The secondary endpoints are change in stimulated whole 
      saliva flow rate, QoL, and composition of saliva. Further secondary endpoints are 
      safety and immune response (human leukocyte antigen (HLA) response) to the stem 
      cells will be assessed. Patients are evaluated at baseline (before treatment), 
      after 4 months, and after 12 months. All study personnel, except study personnel 
      thawing and preparing the treatment for injection, and participants will be 
      blinded to group assignment. Unblinded study personnel will not participate in 
      the outcome assessment. DISCUSSION: The trials will investigate the efficacy and 
      safety of ASC injection to the submandibular gland as a potential new treatment 
      for post-radiation xerostomia. We hope the results will pave the way for a 
      clinically relevant treatment to ameliorate patients with xerostomia, a severely 
      hampering condition. TRIAL REGISTRATION: The study is approved by the Danish Data 
      Protection Agency (protocol number P-2020-1164), the National Ethics Committee 
      protocol number: (Protocol number: 1802872), and the Danish Medical Agency 
      (2018-000348-24). The protocol was registered at the ClinicalTrials.gov database 
      (NCT04776538).
CI  - (c) 2023. BioMed Central Ltd., part of Springer Nature.
FAU - Jakobsen, Kathrine Kronberg
AU  - Jakobsen KK
AUID- ORCID: 0000-0003-0336-5411
AD  - Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, 
      Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark. 
      kathrine.kronberg.jakobsen@regionh.dk.
FAU - Carlander, Amanda-Louise Fenger
AU  - Carlander AF
AD  - Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, 
      Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark.
FAU - Gronhoj, Christian
AU  - Gronhoj C
AD  - Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, 
      Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark.
FAU - Todsen, Tobias
AU  - Todsen T
AD  - Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, 
      Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark.
FAU - Melchiors, Jacob
AU  - Melchiors J
AD  - Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, 
      Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark.
FAU - Paaske, Natasja
AU  - Paaske N
AD  - Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, 
      Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark.
FAU - Madsen, Anne Kathrine Ostergaard
AU  - Madsen AKO
AD  - Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, 
      Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark.
FAU - Kastrup, Jens
AU  - Kastrup J
AD  - Cardiology Stem Cell Centre, The Heart Centre, Rigshospitalet, Copenhagen, 
      Denmark.
FAU - Ekblond, Annette
AU  - Ekblond A
AD  - Cardiology Stem Cell Centre, The Heart Centre, Rigshospitalet, Copenhagen, 
      Denmark.
FAU - Haack-Sorensen, Mandana
AU  - Haack-Sorensen M
AD  - Cardiology Stem Cell Centre, The Heart Centre, Rigshospitalet, Copenhagen, 
      Denmark.
FAU - Farhadi, Mohammad
AU  - Farhadi M
AD  - Department of Oncology, University Hospital Zealand, Roskilde, Denmark.
FAU - Maare, Christian
AU  - Maare C
AD  - Department of Oncology, Herlev Hospital, Herlev, Denmark.
FAU - Friborg, Jeppe
AU  - Friborg J
AD  - Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
FAU - Lynggard, Charlotte Duch
AU  - Lynggard CD
AD  - Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, 
      Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark.
FAU - von Buchwald, Christian
AU  - von Buchwald C
AD  - Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, 
      Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark.
LA  - eng
SI  - ClinicalTrials.gov/NCT04776538
GR  - R198-A9014/Rigshospitalet/
GR  - No grant number/Candys Foundation/
PT  - Clinical Trial Protocol
PT  - Journal Article
DEP - 20230901
PL  - England
TA  - Trials
JT  - Trials
JID - 101263253
SB  - IM
MH  - Humans
MH  - Quality of Life
MH  - Prospective Studies
MH  - *Xerostomia/etiology/therapy
MH  - *Mesenchymal Stem Cells
MH  - *Head and Neck Neoplasms/radiotherapy
MH  - Randomized Controlled Trials as Topic
MH  - Clinical Trials, Phase II as Topic
PMC - PMC10474624
OTO - NOTNLM
OT  - Hyposalivation
OT  - MSC
OT  - Mesenchymal stem cells
OT  - Mesenchymal stromal cells
OT  - Xerostomia
COIS- The authors C.D.L., C.G., and C.V.B. declare the following competing interests: 
      Rigshospitalet and the University of Copenhagen have a pending patent application 
      entitled "Stem cell therapy for salivary gland dysfunction" published as WO 
      2020/165405 A1, with K.K.J, C.D.L., C.G., and C.V.B. as the inventors. The 
      authors A.E., M.H.S. and J.K. declare the following competing interests: A.E., 
      M.H.S. and J.K. are inventors of the patent "Stem cell therapy based on 
      adipose-derived stem cells" (Publication WO 2017-068140). All authors met the 
      ICMJE authorship criteria. No honoraria or payments were made for authorship. The 
      remaining authors declare no competing interests.
EDAT- 2023/09/02 05:42
MHDA- 2023/09/04 06:44
PMCR- 2023/09/01
CRDT- 2023/09/01 23:46
PHST- 2023/05/24 00:00 [received]
PHST- 2023/08/17 00:00 [accepted]
PHST- 2023/09/04 06:44 [medline]
PHST- 2023/09/02 05:42 [pubmed]
PHST- 2023/09/01 23:46 [entrez]
PHST- 2023/09/01 00:00 [pmc-release]
AID - 10.1186/s13063-023-07594-5 [pii]
AID - 7594 [pii]
AID - 10.1186/s13063-023-07594-5 [doi]
PST - epublish
SO  - Trials. 2023 Sep 1;24(1):567. doi: 10.1186/s13063-023-07594-5.