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

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ClinicalTrials.gov Identifier: NCT01548729
Recruitment Status : Completed
First Posted : March 8, 2012
Last Update Posted : March 30, 2021
Sponsor:
Information provided by (Responsible Party):
University Hospital, Strasbourg, France

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.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Diabetes Related Cystic Fibrosis Insulin-dependent Diabetes Procedure: Combined pancreatic islet and lung transplantation Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Metabolic Efficiency of Combined Pancreatic Islet and Lung Transplant for the Treatment of End-Stage Cystic Fibrosis : a Pilot Study
Actual Study Start Date : February 25, 2012
Actual Primary Completion Date : December 20, 2019
Actual Study Completion Date : December 20, 2019


Arm Intervention/treatment
Experimental: Patient with cystic fibrosis
Patients with end-stage cystic fibrosis
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




Primary Outcome Measures :
  1. Metabolic efficiency at 1 year [ Time Frame: 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


Secondary Outcome Measures :
  1. Ratio [C-peptide stimulated T6min/ C-peptide basal T0] [ Time Frame: 1 year after transplant ]
    Δ C peptide = [ C-peptide stimulated T6min/ C-peptide basal T0] Success if Δ C peptide > 2

  2. Ratio [C-peptide/Glucose-Creatinine] & ratio [C-peptide/Glucose] [ Time Frame: Every week during the first month, and every month during 1 year ]
  3. HbA1c [ Time Frame: Every 3 months during 1 year after transplant ]
  4. C-peptide stimulated by glucagon [ Time Frame: Every 3 months during 1 year after transplant ]
  5. Ratio [C-peptide stimulated T6min/ C-peptide basal T0] [ Time Frame: Every 3 months during 1 year after transplant ]
  6. Microalbuminuria & proteinuria [ Time Frame: Every 3 months during 1 year after transplant ]
  7. Insulin requirements [ Time Frame: Every month during 1 year after transplant ]
    Unit/day

  8. Number of minor hypoglycemia [ Time Frame: Every month during 1 year after transplant ]
    defined by a blood glucose level < 0.6g/L at which the patient is capable of self-sugaring

  9. Number of major hypoglycemia [ Time Frame: Every month during 1 year after transplant ]
  10. Glycemic variability (MAGE) [ Time Frame: Every 6 months during 1 year after transplant ]
    by continuous glycemic measurement Holter (CGMS) & glycemic reader memory analysis

  11. duration of hypoglycemia [ Time Frame: Every 6 months during 1 year after transplant ]
    by continuous glycemic measurement Holter (CGMS) & glycemic reader memory analysis

  12. Forced Expiratory Volume (FEV1) [ Time Frame: Every month during 1 year after transplant ]
  13. Forced Vital Capacity (FVC) [ Time Frame: Every month during 1 year after transplant ]
  14. Tiffeneau-Pinelli index [ Time Frame: Every month during 1 year after transplant ]
    FEV1/FVC

  15. Nature of pulmonary infection episodes and nature of acute lung rejection if need be [ Time Frame: Every month during 1 year after transplant ]
  16. Dyspnea score according to the mMRC scale [ Time Frame: Every month during 1 year after transplant ]
  17. Oxygen saturation SaO2 room air [ Time Frame: Every month during 1 year after transplant ]
  18. Median maximum expiration flow [ Time Frame: Every month during 1 year after transplant ]
  19. Number of episodes of pulmonary rejection [ Time Frame: Every visit during 1 year after transplant ]
    requiring a corticosteroid bolus

  20. Number of days of post-transplant hospitalization and during the follow-up [ Time Frame: Every visit during 1 year after transplant ]
  21. Mortality [ Time Frame: Every visit during 1 year after transplant ]
  22. Adverse events [ Time Frame: Every visit during 1 year after transplant ]


Information from the National Library of Medicine

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Ages Eligible for Study:   14 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01548729


Locations
Show Show 28 study locations
Sponsors and Collaborators
University Hospital, Strasbourg, France
Investigators
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Principal Investigator: 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
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Responsible Party: University Hospital, Strasbourg, France
ClinicalTrials.gov Identifier: NCT01548729    
Other Study ID Numbers: 4790
First Posted: March 8, 2012    Key Record Dates
Last Update Posted: March 30, 2021
Last Verified: March 2021
Keywords provided by University Hospital, Strasbourg, France:
Cystic Fibrosis
Diabetes Related Cystic Fibrosis
Lung transplantation
Pancreatic islets
Insulin-dependent diabetes
Additional relevant MeSH terms:
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Cystic Fibrosis
Fibrosis
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Autoimmune Diseases
Immune System Diseases