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

Cystic Fibrosis Clinical Trial

— PIM  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01548729
• Other study ID #: 4790
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 25, 2012
• Est. completion date: December 20, 2019

Study information

• Verified date: March 2021
• Source: University Hospital, Strasbourg, France
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: December 20, 2019
• Est. primary completion date: December 20, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years and older

Eligibility

Inclusion criteria:

• Patient with cystic fibrosis

• Patient able to respect the protocol procedures

• Patient with end-stage respiratory insufficiency indicating a lung transplant

• Clinical history of cystic fibrosis related diabetes and/or insulin-dependent diabetes, with no residual insulin secretion (C-peptide < 0,5 ng/mL) and/or no response to IV glucagon stimulation: [peak stimulated C-peptide (T6min)/basal plasma C-peptide(T0)] < 2. The absence of insulin secretion will be verified 2 times before inclusion

• 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

Non-inclusion criteria:

• 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

• Anemia (hemoglobin Hb <10g / dL in women and Hb <11 g / dL in men), lymphopenia (<1000 / uL), neutropenia (<1500 / uL) or thrombocytopenia (<100,000 / uL).

• Persistent elevated liver enzymes at baseline

• Portal hypertension identified by oesophageal varice and/or hypersplenism (platelets < 120 000 /mm3) or Child-Pugh score > 6.

• Use of a medical treatment under investigation within 4 weeks before inclusion

• All medical situation assessed by an investigator which could interfere with the good management of the project

• Patient restricted of freedom or unable to give his consent

• Patient has been included in another study that could interfere with the results of the study

• Contraindications to the use of experimental drugs (Cellcept®, prednisone, Prograf, prednisolone, methylprednisolone, and pancreatic islets)

Related Conditions & MeSH terms

• Cystic Fibrosis
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes Related Cystic Fibrosis
• Fibrosis
• Insulin-dependent Diabetes

Intervention

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

Locations

Country	Name	City	State
France	CRCM AdulteCHU de Grenoble, Hôpital A. Michallon	Grenoble
France	Nephrologie, CHU Grenoble	Grenoble
France	Réanimation Cardiovasculaire et Thoracique, Hôpital Michallon	Grenoble
France	Service d'Endocrinologie, CHU de Grenoble	Grenoble
France	Service de Chirurgie Cardiaque, CHU Grenoble	Grenoble
France	Service de Pneumologie, Hôpital A. MICHALLON , CHU de Grenoble	Grenoble
France	Service de Radiologie Interventionnelle, CHU de Grenoble	Grenoble
France	CRCM adulte, Centre Hospitalier Lyon-Sud	Lyon
France	Service d'Endocrinologie, Pavillon médical	Lyon
France	Service d'imagerie radiologique et de médecine nucléaire, Centre Hospitalier Lyon-Sud	Lyon
France	Service d'Urologie et chirurgie de la Transplantation, Groupement Hospitalier Edouard Herriot	Lyon
France	Service de Chirurgie Thoracique, HOPITAL LOUIS PRADEL	Lyon
France	Service de médecine de la transplantation et immunologie clinique, Hôpital Edouard Herriot	Lyon
France	Service de pneumologie, Hôpital Louis Pradel	Lyon
France	Service de la Clinique d'Endocrinologie, maladies métaboliques et Nutrition	Nantes
France	Service de Néphrologie et Immuno-transplantation	Nantes
France	Service de Pneumologie	Nantes
France	Service de Radiologie	Nantes
France	Service d'Anesthésie-Réanimations Chirurgicales	Strasbourg
France	Service d'Anesthésie-Réanimations chirurgicales, Nouvel Hôpital Civil	Strasbourg
France	Service d'endocrinologie, diabète et maladies métaboliques	Strasbourg
France	Service de chirurgie, Nouvel Hôpital Civil	Strasbourg
France	Service de pneumologie, Nouvel Hôpital Civil	Strasbourg
France	Service de Radiologie, Hôpital de Hautepierre	Strasbourg
France	Service d'Imagerie - Hôpital Foch	Suresnes
France	Service de Chirurgie Thoracique et Transplantation Pulmonaire - Hôpital Foch	Suresnes
France	Service de Pneumologie - Hôpital Foch	Suresnes
France	Unité d'Endocrinologie, Diabétologie et Médecine Métabolique - Hôpital Foch	Suresnes

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Strasbourg, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Ratio [C-peptide stimulated T6min/ C-peptide basal T0]	? C peptide = [ C-peptide stimulated T6min/ C-peptide basal T0] Success if ? C peptide > 2	1 year after transplant
Secondary	Ratio [C-peptide/Glucose-Creatinine] & ratio [C-peptide/Glucose]		Every week during the first month, and every month during 1 year
Secondary	HbA1c		Every 3 months during 1 year after transplant
Secondary	C-peptide stimulated by glucagon		Every 3 months during 1 year after transplant
Secondary	Ratio [C-peptide stimulated T6min/ C-peptide basal T0]		Every 3 months during 1 year after transplant
Secondary	Microalbuminuria & proteinuria		Every 3 months during 1 year after transplant
Secondary	Insulin requirements	Unit/day	Every month during 1 year after transplant
Secondary	Number of minor hypoglycemia	defined by a blood glucose level < 0.6g/L at which the patient is capable of self-sugaring	Every month during 1 year after transplant
Secondary	Number of major hypoglycemia		Every month during 1 year after transplant
Secondary	Glycemic variability (MAGE)	by continuous glycemic measurement Holter (CGMS) & glycemic reader memory analysis	Every 6 months during 1 year after transplant
Secondary	duration of hypoglycemia	by continuous glycemic measurement Holter (CGMS) & glycemic reader memory analysis	Every 6 months during 1 year after transplant
Secondary	Forced Expiratory Volume (FEV1)		Every month during 1 year after transplant
Secondary	Forced Vital Capacity (FVC)		Every month during 1 year after transplant
Secondary	Tiffeneau-Pinelli index	FEV1/FVC	Every month during 1 year after transplant
Secondary	Nature of pulmonary infection episodes and nature of acute lung rejection if need be		Every month during 1 year after transplant
Secondary	Dyspnea score according to the mMRC scale		Every month during 1 year after transplant
Secondary	Oxygen saturation SaO2 room air		Every month during 1 year after transplant
Secondary	Median maximum expiration flow		Every month during 1 year after transplant
Secondary	Number of episodes of pulmonary rejection	requiring a corticosteroid bolus	Every visit during 1 year after transplant
Secondary	Number of days of post-transplant hospitalization and during the follow-up		Every visit during 1 year after transplant
Secondary	Mortality		Every visit during 1 year after transplant
Secondary	Adverse events		Every visit during 1 year after transplant