Treatment of Patients With Teduglutide (GLP-2) for GVHD and Analysis of Paneth Cells of GVHD Patients

Graft Versus Host Disease Clinical Trial

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04290429
• Other study ID #: GLP-2 in GVHD
• Status: Completed
• Phase: Early Phase 1
• Start date: December 6, 2017
• Est. completion date: December 6, 2019

Study information

• Verified date: November 2023
• Source: University of Freiburg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: December 6, 2019
• Est. primary completion date: December 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Drug:
• Teduglutide
Treatment of patients with SR-GI-GVHD with teduglutide

Locations

Country	Name	City	State
Germany	Medical Center University of Freiburg	Freiburg	Baden Württemberg

Sponsors (1)

Lead Sponsor	Collaborator
University of Freiburg

Country where clinical trial is conducted

Germany, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Paneth cell numbers	Quantification of Paneth cell numbers within the intestinal crypts before and during teduglutide treatment.	2 years
Secondary	Stool frequency	Analysis of patient's stool frequency before and during teduglutide treatment.	2 years
Secondary	Intestinal absorption	Analysis of patient's albumin serum levels before and during teduglutide treatment.	2 years