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

• Sponsor: University of Freiburg (Other)
• Overall Status: Completed
• CT.gov ID: NCT04290429
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arm: 1
• Actual Duration (Months): 24
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease	Drug: Teduglutide	Early Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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).
• Actual Study Start Date: Dec 6, 2017
• Actual Primary Completion Date: Dec 6, 2019
• Actual Study Completion Date: Dec 6, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SR-GI-GVHD Analysis of patient's stool frequency, albumin serum levels and quantification of Paneth cell numbers in GI biopsies before and during teduglutide treatment.	Drug: Teduglutide; Treatment of patients with SR-GI-GVHD with teduglutide

Outcome Measures

Primary Outcome Measures

1. Paneth cell numbers [2 years]

   Quantification of Paneth cell numbers within the intestinal crypts before and during teduglutide treatment.

Secondary Outcome Measures

1. Stool frequency [2 years]

   Analysis of patient's stool frequency before and during teduglutide treatment.

2. Intestinal absorption [2 years]

   Analysis of patient's albumin serum levels before and during teduglutide treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical Center University of Freiburg	Freiburg	Baden Württemberg	Germany	79106

Sponsors and Collaborators

• University of Freiburg

Investigators

• Principal Investigator: Robert Zeiser, Prof. Dr., Medical Center University of Freiburg

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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. Review.
• 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.
• 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.
• 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. Review.

• Responsible Party: Robert Zeiser, Director of the Division of Tumor Immunology, University of Freiburg
• ClinicalTrials.gov Identifier: NCT04290429
• Other Study ID Numbers: GLP-2 in GVHD
• First Posted: Mar 2, 2020
• Last Update Posted: Mar 2, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Graft vs Host Disease; Teduglutide

Study Results

No Results Posted as of Mar 2, 2020