Clinical trial NCT04290429: Treatment of Patients With Teduglutide (GLP-2) for GVHD and Analysis of Paneth Cells of GVHD Patients
Official title: Analysis of the Effect of Teduglutide Treatment on Intestinal Malabsorption and Paneth Cell Numbers in Patients With Steroid-refractory Gastrointestinal Graft Versus Host Disease (SR-GI-GVHD).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Graft Versus Host Disease
Lead sponsor: University of Freiburg
Sponsor class: OTHER
First posted: 2020-03-02
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this study the investigators evaluate the outcomes of six steroid-refractory GVHD patients with gastrointestinal signs of GVHD that were treated with teduglutide.

Detailed description: Preliminary studies have showed that Glucagon-like peptide 2 (GLP-2) has regenerative and protective effects on the gastrointestinal tract after bowel injury. It induces positive effects in the GI tract like nutrient uptake, mucosal growth, protection from inflammation, etc. One of the target organs from GVHD is the GI tract, and since patients suffering from GI-GVHD experience intestinal disorders like loss of mucosal epithelial integrity, diarrhea accompanied by strong abdominal pain that can lead to food inanition, the investigators therefore aimed to examine the outcome of patients suffering from SR-GI-GVHD that are treated with the GLP-2 analogue, Teduglutide. The investigators will determine the outcome of each patient by monitoring the gastrointestinal signs like diarrhea frequency, intestinal absorption measured by serum-albumin concentrations and GI histology, specifically the number of Paneth cells before and during teduglutide treatment.

Eligibility criteria: Inclusion Criteria:

* Patients with signs of acute SR-GI-GVHD
* Age ≥ 18 years
* Peripheral blood and stool samples available before and during treatment
* Written informed consent
* Ability to understand the nature of the study and the study related procedures and to comply with them

Exclusion Criteria:

* Age ≤ 18 years
* Lack of informed consent

Primary outcomes:
measure: Paneth cell numbers
timeFrame: 2 years
Secondary outcomes:
measure: Stool frequency
timeFrame: 2 years
measure: Intestinal absorption
timeFrame: 2 years
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Medical Center University of Freiburg
state: Baden Württemberg
Study officials:
affiliation: Medical Center University of Freiburg
name: Robert Zeiser, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zeiser R, Blazar BR. Acute Graft-versus-Host Disease - Biologic Process, Prevention, and Therapy. N Engl J Med. 2017 Nov 30;377(22):2167-2179. doi: 10.1056/NEJMra1609337. No abstract available.
citation: Drucker DJ, Yusta B. Physiology and pharmacology of the enteroendocrine hormone glucagon-like peptide-2. Annu Rev Physiol. 2014;76:561-83. doi: 10.1146/annurev-physiol-021113-170317. Epub 2013 Oct 25.
citation: Drucker DJ, Erlich P, Asa SL, Brubaker PL. Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7911-6. doi: 10.1073/pnas.93.15.7911.
citation: Boushey RP, Yusta B, Drucker DJ. Glucagon-like peptide (GLP)-2 reduces chemotherapy-associated mortality and enhances cell survival in cells expressing a transfected GLP-2 receptor. Cancer Res. 2001 Jan 15;61(2):687-93.
citation: Jeppesen PB, Hartmann B, Thulesen J, Graff J, Lohmann J, Hansen BS, Tofteng F, Poulsen SS, Madsen JL, Holst JJ, Mortensen PB. Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon. Gastroenterology. 2001 Mar;120(4):806-15. doi: 10.1053/gast.2001.22555.
citation: Jeppesen PB, Pertkiewicz M, Messing B, Iyer K, Seidner DL, O'keefe SJ, Forbes A, Heinze H, Joelsson B. Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology. 2012 Dec;143(6):1473-1481.e3. doi: 10.1053/j.gastro.2012.09.007. Epub 2012 Sep 11.