Cystic FibrosisPhase 1/2PIMNCT01548729
Metabolic Efficiency of Combined Pancreatic Islet and Lung Transplant for the Treatment of End-Stage Cystic Fibrosis
A Phase 1/2 study testing Combined pancreatic islet and lung transplantation in people with Cystic Fibrosis and Diabetes Related Cystic Fibrosis, run by University Hospital, Strasbourg, France at 28 sites in France.
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. Read more about this study
- Who is it for?
- Ages 14 years and older
- Conditions the study is for
- Cystic Fibrosis, Diabetes Related Cystic Fibrosis, Insulin-dependent Diabetes
- What is being tested?
- Combined pancreatic islet and lung transplantation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 28 sitesFrance
- Study dates
- 25 Feb 2012to 20 Dec 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Show all 25Show fewer
- 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)
Who cannot join
None listed.
Trial locations and contacts
28 sites in 1 country.
28 sites in 1 country
France28 sites
CRCM AdulteCHU de Grenoble, Hôpital A. Michallon
Grenoble, 38 043
Nephrologie, CHU Grenoble
Grenoble, 38043
Réanimation Cardiovasculaire et Thoracique, Hôpital Michallon
Grenoble, 38043
Service d'Endocrinologie, CHU de Grenoble
Grenoble, 38043
Service de Chirurgie Cardiaque, CHU Grenoble
Grenoble, 38043
Service de Radiologie Interventionnelle, CHU de Grenoble
Grenoble, 38043
Service de Pneumologie, Hôpital A. MICHALLON , CHU de Grenoble
Grenoble, 38700
Service d'Urologie et chirurgie de la Transplantation, Groupement Hospitalier Edouard Herriot
Lyon, 69 437
Service de médecine de la transplantation et immunologie clinique, Hôpital Edouard Herriot
Lyon, 69437
CRCM adulte, Centre Hospitalier Lyon-Sud
Lyon, 69495
Service d'Endocrinologie, Pavillon médical
Lyon, 69495
Service d'imagerie radiologique et de médecine nucléaire, Centre Hospitalier Lyon-Sud
Lyon, 69495
Service de Chirurgie Thoracique, HOPITAL LOUIS PRADEL
Lyon, 69677
Service de pneumologie, Hôpital Louis Pradel
Lyon, 69677
Service de la Clinique d'Endocrinologie, maladies métaboliques et Nutrition
Nantes, 44093
Service de Néphrologie et Immuno-transplantation
Nantes, 44093
Service de Pneumologie
Nantes, 44093
Service de Radiologie
Nantes, 44093
Service d'endocrinologie, diabète et maladies métaboliques
Strasbourg, 67 091
Service d'Anesthésie-Réanimations chirurgicales, Nouvel Hôpital Civil
Strasbourg, 67091
Service d'Anesthésie-Réanimations Chirurgicales
Strasbourg, 67091
Service de chirurgie, Nouvel Hôpital Civil
Strasbourg, 67091
Service de pneumologie, Nouvel Hôpital Civil
Strasbourg, 67091
Service de Radiologie, Hôpital de Hautepierre
Strasbourg, 67098
Unité d'Endocrinologie, Diabétologie et Médecine Métabolique - Hôpital Foch
Suresnes, 92150
Service d'Imagerie - Hôpital Foch
Suresnes, 92151
Service de Chirurgie Thoracique et Transplantation Pulmonaire - Hôpital Foch
Suresnes, 92151
Service de Pneumologie - Hôpital Foch
Suresnes, 92151
About this study
Official title: Metabolic Efficiency of Combined Pancreatic Islet and Lung Transplant for the Treatment of End-Stage Cystic Fibrosis : a Pilot Study
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.
- Being tested
- Combined pancreatic islet and lung transplantation
- Keywords
- Cystic Fibrosis, Diabetes Related Cystic Fibrosis, Lung transplantation, Pancreatic islets, Insulin-dependent diabetes
- Medical subject headings
- Cystic Fibrosis, Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combined pancreatic islet and lung transplantationProcedure or surgery
Combined pancreatic islet and lung transplant from the same donor for the treatment of patients with end-stage cystic fibrosis
| Study group | Role | What they receive |
|---|---|---|
| Patient with cystic fibrosis | Experimental | Patients with end-stage cystic fibrosis Receives: Procedure: Combined pancreatic islet and lung transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 year
Secondary outcomes (22)
Ratio [C-peptide stimulated T6min/ C-peptide basal T0]
Δ C peptide = [ C-peptide stimulated T6min/ C-peptide basal T0] Success if Δ C peptide > 2
Measured: 1 year after transplant
Ratio [C-peptide/Glucose-Creatinine] & ratio [C-peptide/Glucose]
Measured: Every week during the first month, and every month during 1 year
HbA1c
Measured: Every 3 months during 1 year after transplant
C-peptide stimulated by glucagon
Measured: Every 3 months during 1 year after transplant
Ratio [C-peptide stimulated T6min/ C-peptide basal T0]
Measured: Every 3 months during 1 year after transplant
Microalbuminuria & proteinuria
Measured: Every 3 months during 1 year after transplant
Insulin requirements
Unit/day
Measured: Every month during 1 year after transplant
Number of minor hypoglycemia
defined by a blood glucose level < 0.6g/L at which the patient is capable of self-sugaring
Measured: Every month during 1 year after transplant
Number of major hypoglycemia
Measured: Every month during 1 year after transplant
Glycemic variability (MAGE)
by continuous glycemic measurement Holter (CGMS) \& glycemic reader memory analysis
Measured: Every 6 months during 1 year after transplant
duration of hypoglycemia
by continuous glycemic measurement Holter (CGMS) \& glycemic reader memory analysis
Measured: Every 6 months during 1 year after transplant
Forced Expiratory Volume (FEV1)
Measured: Every month during 1 year after transplant
Forced Vital Capacity (FVC)
Measured: Every month during 1 year after transplant
Tiffeneau-Pinelli index
FEV1/FVC
Measured: Every month during 1 year after transplant
Nature of pulmonary infection episodes and nature of acute lung rejection if need be
Measured: Every month during 1 year after transplant
Dyspnea score according to the mMRC scale
Measured: Every month during 1 year after transplant
Oxygen saturation SaO2 room air
Measured: Every month during 1 year after transplant
Median maximum expiration flow
Measured: Every month during 1 year after transplant
Number of episodes of pulmonary rejection
requiring a corticosteroid bolus
Measured: Every visit during 1 year after transplant
Number of days of post-transplant hospitalization and during the follow-up
Measured: Every visit during 1 year after transplant
Mortality
Measured: Every visit during 1 year after transplant
Adverse events
Measured: Every visit during 1 year after transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2012 (estimated)
- Study start25 Feb 2012
- Primary completion20 Dec 2019
- Study completion20 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by University Hospital, Strasbourg, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Strasbourg, France
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Laurence KESSLER, MD, PhD, Principal investigator, Hôpitaux Universitaires de StrasbourgPierre Yves BENHAMOU, MD, phD, Principal investigator, University Hospital, GrenobleDominique Grenet, MD, Principal investigator, HOPITAL FOCH DE SURESNESCharles THIVOLET, MD, Principal investigator, Hospices Civils de LyonThierry BERNEY, MD PhD, Principal investigator, CENTRE ROMAND DE TRANSPLANTATION - SUISSE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01548729
- Sponsor's protocol ID
- 4790
- Acronym
- PIM
- Status last verified
- Mar 2021
- First submitted
- 10 Feb 2012
- Last updated
- 30 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 35403818
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Efficiency of Combined Pancreatic Islet and Lung Transplant for the Treatment of End-Stage Cystic Fibrosis : a Pilot Study
- ClinicalTrials.gov ID
- NCT01548729
- Acronym / sponsor ID
- PIM / 4790
- Keywords
- Cystic Fibrosis, Diabetes Related Cystic Fibrosis, Lung transplantation, Pancreatic islets, Insulin-dependent diabetes
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University Hospital, Strasbourg, FranceUniversity, hospital or other
- Study start
- 25 Feb 2012 (actual)
- Primary completion
- 20 Dec 2019 (actual)
- Study completion
- 20 Dec 2019 (actual)
- First posted
- 8 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patient with cystic fibrosis | Experimental | Procedure: Combined pancreatic islet and lung transplantationPatients with end-stage cystic fibrosis |
Who may qualify
- Ages
- 14 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (25 listed)
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combined pancreatic islet and lung transplantationCombined pancreatic islet and lung transplant from the same donor for the treatment of patients with end-stage cystic fibrosis | Procedure or surgery | Patient with cystic fibrosis |
Primary outcome
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
22 secondary outcomes
Ratio [C-peptide stimulated T6min/ C-peptide basal T0]
Time frame: 1 year after transplant
Ratio [C-peptide/Glucose-Creatinine] & ratio [C-peptide/Glucose]
Time frame: Every week during the first month, and every month during 1 year
HbA1c
Time frame: Every 3 months during 1 year after transplant
C-peptide stimulated by glucagon
Time frame: Every 3 months during 1 year after transplant
Ratio [C-peptide stimulated T6min/ C-peptide basal T0]
Time frame: Every 3 months during 1 year after transplant
Microalbuminuria & proteinuria
Time frame: Every 3 months during 1 year after transplant
Insulin requirements
Time frame: Every month during 1 year after transplant
Number of minor hypoglycemia
Time frame: Every month during 1 year after transplant
Number of major hypoglycemia
Time frame: Every month during 1 year after transplant
Glycemic variability (MAGE)
Time frame: Every 6 months during 1 year after transplant
duration of hypoglycemia
Time frame: Every 6 months during 1 year after transplant
Forced Expiratory Volume (FEV1)
Time frame: Every month during 1 year after transplant
Forced Vital Capacity (FVC)
Time frame: Every month during 1 year after transplant
Tiffeneau-Pinelli index
Time frame: Every month during 1 year after transplant
Nature of pulmonary infection episodes and nature of acute lung rejection if need be
Time frame: Every month during 1 year after transplant
Dyspnea score according to the mMRC scale
Time frame: Every month during 1 year after transplant
Oxygen saturation SaO2 room air
Time frame: Every month during 1 year after transplant
Median maximum expiration flow
Time frame: Every month during 1 year after transplant
Number of episodes of pulmonary rejection
Time frame: Every visit during 1 year after transplant
Number of days of post-transplant hospitalization and during the follow-up
Time frame: Every visit during 1 year after transplant
Mortality
Time frame: Every visit during 1 year after transplant
Adverse events
Time frame: Every visit during 1 year after transplant
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2021.
- Derived from this study: PubMed 35403818Rakotoarisoa 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laurence KESSLER, MD, PhD principal investigator
Hôpitaux Universitaires de Strasbourg
Pierre Yves BENHAMOU, MD, phD principal investigator
University Hospital, Grenoble
Dominique Grenet, MD principal investigator
HOPITAL FOCH DE SURESNES
28 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Combined pancreatic islet and lung transplantation in people with Cystic Fibrosis and Diabetes Related Cystic Fibrosis, run by University Hospital, Strasbourg, France at 28 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metabolic efficiency at 1 year (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01548729, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2021.