Metabolic Efficiency of Combined Pancreatic Islet and Lung Transplant for the Treatment of End-Stage Cystic Fibrosis

NCT01548729 | Completed Phase 1 DMC

• 1 other identifier: 4790
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 28

Brief Summary

Patients with end-stage cystic fibrosis (CF) and severe CF-related diabetes (CFRD) may benefit from combined lung-pancreatic islet transplantation. A recent case series showed that combined bilateral lung and pancreatic islet transplantation is a viable therapeutic option for patients with end-stage CF and CFRD. The use of different organs from a single donor may lead to reduced immunogenicity. As the prevalence of CFRD has increased dramatically with the improved life expectancy of patients with CF, islet transplantation should be considered at the end-stage CF. By restoring metabolic control, the investigators hypothesize that islet transplantation may improve the management of CF patients undergoing lung transplant and decrease the complication rate in the early postoperative period.

Conditions

Cystic Fibrosis; Diabetes Related Cystic Fibrosis; Insulin-dependent Diabetes

Keywords

Cystic Fibrosis; Diabetes Related Cystic Fibrosis; Lung transplantation; Pancreatic islets; Insulin-dependent diabetes

Outcome Measures

Primary Outcomes (1)

• Metabolic efficiency at 1 year

  Combined criteria based on the 4 following criteria: weight increase \> 5% compared to inclusion, fasting blood glucose \< 1.1 g/l at 12 months post-transplant (beta score criterion), Reducing insulin requirements (expressed in UI/day) compared to inclusion \& decreased in HbA1c \>= 0.5% (in absolute value) compared to inclusion Success is defined by achieving at least three of these criteria

  1 year

Secondary Outcomes (22)

• Ratio [C-peptide stimulated T6min/ C-peptide basal T0]

  1 year after transplant

• Ratio [C-peptide/Glucose-Creatinine] & ratio [C-peptide/Glucose]

  Every week during the first month, and every month during 1 year

• HbA1c

  Every 3 months during 1 year after transplant

• C-peptide stimulated by glucagon

  Every 3 months during 1 year after transplant

• Ratio [C-peptide stimulated T6min/ C-peptide basal T0]

  Every 3 months during 1 year after transplant

Study Arms (1)

Patient with cystic fibrosis

EXPERIMENTAL

Patients with end-stage cystic fibrosis

Procedure: Combined pancreatic islet and lung transplantation

Interventions

Combined pancreatic islet and lung transplantation PROCEDURE

Combined pancreatic islet and lung transplant from the same donor for the treatment of patients with end-stage cystic fibrosis

Patient with cystic fibrosis

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with cystic fibrosis
• Patient able to respect the protocol procedures
• Patient with end-stage respiratory insufficiency indicating a lung transplant
• Evolution of diabetes for over 3 years
• Patient whose glycaemic control obtained with insulin therapy is not satisfactory and could significantly alter quality of life (HbA1c \> 7% and/or MAGE index \> 1,25). This situation is assessed by a diabetologist.
• Social Security membership or benefit from Social Welfare
• Patient who received the results of the medical evaluation required
• Patient with contra-indication for undergo a lung transplant
• Patient with an indication of heart, liver or kidney transplantation
• Patient for which poor therapeutic compliance is expected
• Patient under oral antidiabetic drug
• In women of childbearing potential: pregnancy test (urine and / or blood) positive, lactation, or unwilling to use effective contraception for the duration of the study until 3 months after the end . Men: procreation project during the study period up to 3 months after its end, or unwilling to use effective contraception patient.
• Active infection, including hepatitis B, hepatitis C, HIV
• Any history of malignancy within the past 5 years, with the exception of cutaneous basal cell carcinomas completely resected. The history of breast or melanoma cancers are an absolute contraindication
• Alcoholic intoxication or drug addiction

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

Study Sites (28)

CRCM AdulteCHU de Grenoble, Hôpital A. Michallon

Grenoble, 38 043, France

Location

Nephrologie, CHU Grenoble

Grenoble, 38043, France

Location

Réanimation Cardiovasculaire et Thoracique, Hôpital Michallon

Grenoble, 38043, France

Location

Service d'Endocrinologie, CHU de Grenoble

Grenoble, 38043, France

Location

Service de Chirurgie Cardiaque, CHU Grenoble

Grenoble, 38043, France

Location

Service de Radiologie Interventionnelle, CHU de Grenoble

Grenoble, 38043, France

Location

Service de Pneumologie, Hôpital A. MICHALLON , CHU de Grenoble

Grenoble, 38700, France

Location

Service d'Urologie et chirurgie de la Transplantation, Groupement Hospitalier Edouard Herriot

Lyon, 69 437, France

Location

Service de médecine de la transplantation et immunologie clinique, Hôpital Edouard Herriot

Lyon, 69437, France

Location

CRCM adulte, Centre Hospitalier Lyon-Sud

Lyon, 69495, France

Location

Service d'Endocrinologie, Pavillon médical

Lyon, 69495, France

Location

Service d'imagerie radiologique et de médecine nucléaire, Centre Hospitalier Lyon-Sud

Lyon, 69495, France

Location

Service de Chirurgie Thoracique, HOPITAL LOUIS PRADEL

Lyon, 69677, France

Location

Service de pneumologie, Hôpital Louis Pradel

Lyon, 69677, France

Location

Service de la Clinique d'Endocrinologie, maladies métaboliques et Nutrition

Nantes, 44093, France

Location

Service de Néphrologie et Immuno-transplantation

Nantes, 44093, France

Location

Service de Pneumologie

Nantes, 44093, France

Location

Service de Radiologie

Nantes, 44093, France

Location

Service d'endocrinologie, diabète et maladies métaboliques

Strasbourg, 67 091, France

Location

Service d'Anesthésie-Réanimations chirurgicales, Nouvel Hôpital Civil

Strasbourg, 67091, France

Location

Service d'Anesthésie-Réanimations Chirurgicales

Strasbourg, 67091, France

Location

Service de chirurgie, Nouvel Hôpital Civil

Strasbourg, 67091, France

Location

Service de pneumologie, Nouvel Hôpital Civil

Strasbourg, 67091, France

Location

Service de Radiologie, Hôpital de Hautepierre

Strasbourg, 67098, France

Location

Unité d'Endocrinologie, Diabétologie et Médecine Métabolique - Hôpital Foch

Suresnes, 92150, France

Location

Service d'Imagerie - Hôpital Foch

Suresnes, 92151, France

Location

Service de Chirurgie Thoracique et Transplantation Pulmonaire - Hôpital Foch

Suresnes, 92151, France

Location

Service de Pneumologie - Hôpital Foch

Suresnes, 92151, France

Location

Related Publications (1)

• Rakotoarisoa L, Wagner C, Munch M, Renaud Picard B, Grenet D, Olland A, Greget M, Enescu I, Bouilloud F, Bonnette P, Guth A, Bosco D, Mercier C, Rabilloud M, Berney T, Yves Benhamou P, Massard G, Camilo C, Colin C, Arnold C, Kessler R, Kessler L; GRAGIL-TREPID Group. Feasibility and efficacy of combined pancreatic islet-lung transplantation in cystic fibrosis-related diabetes-PIM study: A multicenter phase 1-2 trial. Am J Transplant. 2022 Jul;22(7):1861-1872. doi: 10.1111/ajt.17058. Epub 2022 Apr 26.

  PMID: 35403818 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis; Diabetes Mellitus, Type 1

Interventions

Lung Transplantation

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pulmonary Surgical Procedures; Thoracic Surgical Procedures; Surgical Procedures, Operative; Organ Transplantation; Transplantation

Study Officials

• Laurence KESSLER, MD, PhD

  Hôpitaux Universitaires de Strasbourg

  PRINCIPAL INVESTIGATOR

• Pierre Yves BENHAMOU, MD, phD

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

• Dominique Grenet, MD

  HOPITAL FOCH DE SURESNES

  PRINCIPAL INVESTIGATOR

• Charles THIVOLET, MD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

• Thierry BERNEY, MD PhD

  CENTRE ROMAND DE TRANSPLANTATION - SUISSE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2012
• First Posted: March 8, 2012
• Study Start: February 25, 2012
• Primary Completion: December 20, 2019
• Study Completion: December 20, 2019
• Last Updated: March 30, 2021

Record last verified: 2021-03

Locations

FR (28)