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Targeting CXCR1/2 Does Not Improve Insulin Secretion After Pancreatic Islet Transplantation: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial in Type 1 Diabetes
- Source :
- Diabetes Care
- Publication Year :
- 2020
- Publisher :
- American Diabetes Association, 2020.
-
Abstract
- OBJECTIVE Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients. RESEARCH DESIGN AND METHODS A phase 3, multicenter, randomized, double-blind, parallel-assignment study (NCT01817959) was conducted in recipients of islet allotransplants randomized (2:1) to reparixin or placebo in addition to immunosuppression. Primary outcome was the area under the curve (AUC) for C-peptide during the mixed-meal tolerance test at day 75 ± 5 after the first and day 365 ± 14 after the last transplant. Secondary end points included insulin independence and standard measures of glycemic control. RESULTS The intention-to-treat analysis did not show a significant difference in C-peptide AUC at both day 75 (27 on reparixin vs. 18 on placebo, P = 0.99) and day 365 (24 on reparixin vs. 15 on placebo, P = 0.71). There was no statistically significant difference between treatment groups at any time point for any secondary variable. Analysis of patient subsets showed a trend for a higher percentage of subjects retaining insulin independence for 1 year after a single islet infusion in patients receiving reparixin as compared with patients receiving placebo (26.7% vs. 0%, P = 0.09) when antithymocyte globulin was used as induction immunosuppression. CONCLUSIONS In this first double-blind randomized trial, islet transplantation data obtained with reparixin do not support a role of CXCR1/2 inhibition in preventing islet inflammation-mediated damage.
- Subjects :
- Male
Time Factors
Endocrinology, Diabetes and Metabolism
Islets of Langerhans Transplantation
Placebo-controlled study
Gastroenterology
Receptors, Interleukin-8B
Receptors, Interleukin-8A
law.invention
Placebos
0302 clinical medicine
Randomized controlled trial
law
Insulin Secretion
Postoperative Period
030212 general & internal medicine
Sulfonamides
geography.geographical_feature_category
Clinical Care/Education/Nutrition/Psychosocial Research
Area under the curve
Middle Aged
Islet
Combined Modality Therapy
Female
Immunosuppressive Agents
Adult
medicine.medical_specialty
Adolescent
030209 endocrinology & metabolism
Placebo
Drug Administration Schedule
Young Adult
Islets of Langerhans
03 medical and health sciences
Double-Blind Method
Internal medicine
CXCR1/2, insulin secretion, pancreatic islet transplantation
Internal Medicine
medicine
Humans
Aged
Advanced and Specialized Nursing
geography
Type 1 diabetes
business.industry
medicine.disease
Transplantation
Diabetes Mellitus, Type 1
Pancreatic islet transplantation
business
Subjects
Details
- ISSN :
- 19355548 and 01495992
- Volume :
- 43
- Database :
- OpenAIRE
- Journal :
- Diabetes Care
- Accession number :
- edsair.doi.dedup.....d89a6b73c2fc9e156aa92795c8aa2f03