Type 1 Diabetes MellitusPhase 1/2NCT00321256
Human Islet Transplantation in Brittle Type 1 Diabetes Mellitus. The GRAGIL 2 Study.
A Phase 1/2 study testing human pancreatic islet transplantation in people with Type 1 Diabetes Mellitus, run by University Hospital, Grenoble at 6 sites in 2 countries.
Trial summary
This research project is supported by a multicentric network of collaborators whose goal is to assess the efficacy of transplanting allogenic pancreas islets to restore insulin secretion in patients with brittle type 1, insulin-dependent diabetes mellitus and to improve their metabolic control. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- human pancreatic islet transplantation
- Type of treatment
- Surgery or procedure
- How many people
- 22 participants
- Where
- 6 sitesin 2 countries
- Study dates
- Jul 2003to Jul 2007
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 1 diabetes mellitus
- Disease duration > 5 years
- Despite intensive insulin therapy with tight endocrinologist supervision, persistence of the following conditions : hypoglycemia unawareness (< 54 mg/dl) ; brittleness with at least two episodes of severe hypoglycemia ((defined by the need for assistance to correct the blood glucose level) or ketoacidosis per year , or often enough that the diabetologist judges the frequency to be life-threatening, the risk of transplantation and immunosuppression being judged to be less than the risk of the spontaneous course of uncontrolled diabetes
- Basal and stimulated plasma C-peptide < 0.2 ng/ml
- Creatinine clearance ≥ 50 ml/min/1.73 m2 and proteinuria < 0.5 g/24h
Who cannot join
- Severe cardiovascular disease (recent myocardial infarction, unstable coronaropathy…)
- Severe systemic infection, including hepatitis C or B viral infection, HIV infection or tuberculosis
- Past or present neoplasia (with the exception of non melanoma skin cancers)
- Body weight > 70 kg in women and BW > 75 kg in men or BMI > 26
- Stimulated C-peptide ≥ 0.3 ng/ml upon Glucagon or Arginine stimulation
- Age < 18 years or > 65 years
Show all 26Show fewer
- Creatinine clearance < 50 ml/min/1.73 m2
- Albuminuria > 300 mg /24h or proteinuria > 0.5 g/24h
- Hemoglobinemia < 120 g/l in women or < 130 g/l in men
- Liver disease (enzymes > 1.5 N) such as cirrhosis or hepatitis
- Liver hemangioma
- Untreated proliferating diabetic retinopathy
- Pregnancy, lactation, pregnancy project or absence of efficient contraception
- Previous transplantation or immunization as judged by anti-HLA antibodies (> 20%)
- Insulin needs > 0.7 IU/kg/d or > 50 IU
- HbA1c > 12 %
- Any medical condition needing the chronic use of steroids
- Addison disease
- Any hemostasis disorder needing a prolonged treatment with anticoagulation drugs. Low-dose aspirin is permitted. coagulation disorders contraindicating the procedure, such as platelet count < 100000/mm3.
- Serious life-threatening disease
- Medical or surgical history potentially influencing the absorption, distribution, metabolism and clearance of drugs
- Uncontrolled hypercholesterolemia (> 350 mg/dl, 9.1 mmol/l) or hypertriglyceridemia (> 500 mg/dl, 5.6 mmol/l)
- Leukocytes < 4500/mm3, neutrophils < 2000/mm3, platelets < 100000/mm3
- Any medical or psychosocial condition susceptible to interfere with the study, such as drug abuse or recent alcohol abuse
- Poor therapeutic observance
- Failure to communicate or cooperate with the investigator
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
France5 sites
University Hospital, Department of Endocrinology
Besançon, 25000
University Hospital, Department of Endocrinology
Grenoble, 38043
University Hospital, Department of Endocrinology
Lyon, 69000
University Hospital, Department of Endocrinology
Montpellier, 34000
University Hospital, Department of Endocrinology
Strasbourg, 66000
About this study
Official title: Transplantation d'Ilots Pancreatiques Allogeniques Adultes Pour le Traitement du Diabete Insulino-dependant: Etude GRAGIL 2.
This research project is supported by a multicentric network of collaborators whose goal is to assess the efficacy of transplanting allogenic pancreas islets to restore insulin secretion in patients with brittle type 1, insulin-dependent diabetes mellitus and to improve their metabolic control.
Read the detailed description
The general objective is to demonstrate the beneficial effect of islet allotransplantation in patients with brittle type 1 diabetes with no endogenous insulin secretion, for whom the risk of the spontaneous course of the disease is judged to be worse than the transplantation-related risk. The specific objective is to establish reference data for islet transplantation in non-uremic patients with brittle diabetes, in a multicentric network setting, using the Edmonton protocol.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- human pancreatic islet transplantation
- Keywords
- islet transplantation, brittle diabetes, severe hypoglycemia, type 1 diabetes mellitus
- Medical subject headings
- Diabetes Mellitus, Type 1, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
human pancreatic islet transplantationProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
The rate of insulin-independence, judged upon the following criteria : HbA1c < 6.1%,
post-prandial blood glucose < 180 mg/dl, mean amplitude of glycemic excursion (MAGE index)
< 60 mg/dl, basal C-peptide > 0.5 ng/ml. This insulin independent rate will be assessed 6 months
and 12 months following transplantation.
Secondary outcomes (3)
The rate of success according to the DiaCell composite score defined by the following 4 items : functional islet graft, defined by a basal C-peptide > 0.5 ng/ml;
good metabolic control, defined by HbA1c ≤ 6.5%; disappearance of hypoglycemic events; reduction in exogenous insulin needs ≥ 30%.
Morbidity and quality of life will also be assessed.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2006 (estimated)
- Study startJul 2003
- Study completionJul 2007
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 Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Collaborators
- Alfediam
- Investigators
- Pierre Y Benhamou, MD, PhD, Principal investigator, Universty Hospital, Grenoble, FrancePhilippe Morel, MD, PhD, Study chair, University Hospital, Geneva, SwitzerlandCharles Thivolet, MD, PhD, Study director, Hospices Civils de LyonAlfred Penfornis, MD, PhD, Study director, University Hospital, Besancon, FranceLaurence Kessler, MD, PhD, Study director, University Hospital, Strasbourg, FranceEric Renard, MD, PhD, Study director, University Hospital, Montpellier FranceLionel Badet, MD, PhD, Study director, Hospices Civils de LyonCyrille Colin, MD, PhD, Study director, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00321256
- Sponsor's protocol ID
- 011226/DGS-2001/0195
- Status last verified
- Mar 2012
- First submitted
- 2 May 2006
- Last updated
- 2 Mar 2012
- Results posted
- No
Publications
Lablanche S, Borot S, Wojtusciszyn A, Bayle F, Tetaz R, Badet L, Thivolet C, Morelon E, Frimat L, Penfornis A, Kessler L, Brault C, Colin C, Tauveron I, Bosco D, Berney T, Benhamou PY; GRAGIL Network. Five-Year Metabolic, Functional, and Safety Results of Patients With Type 1 Diabetes Transplanted With Allogenic Islets Within the Swiss-French GRAGIL Network. Diabetes Care. 2015 Sep;38(9):1714-22. doi: 10.2337/dc15-0094. Epub 2015 Jun 11.
PubMed 26068866
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transplantation d'Ilots Pancreatiques Allogeniques Adultes Pour le Traitement du Diabete Insulino-dependant: Etude GRAGIL 2.
- ClinicalTrials.gov ID
- NCT00321256
- Acronym / sponsor ID
- 011226/DGS-2001/0195
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- islet transplantation, brittle diabetes, severe hypoglycemia, type 1 diabetes mellitus
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Collaborators
- Alfediam
- Study start
- Jul 2003
- Study completion
- Jul 2007 (actual)
- First posted
- 3 May 2006 (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.
This research project is supported by a multicentric network of collaborators whose goal is to assess the efficacy of transplanting allogenic pancreas islets to restore insulin secretion in patients with brittle type 1, insulin-dependent diabetes mellitus and to improve their metabolic control.
Detailed description
The general objective is to demonstrate the beneficial effect of islet allotransplantation in patients with brittle type 1 diabetes with no endogenous insulin secretion, for whom the risk of the spontaneous course of the disease is judged to be worse than the transplantation-related risk. The specific objective is to establish reference data for islet transplantation in non-uremic patients with brittle diabetes, in a multicentric network setting, using the Edmonton protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Type 1 diabetes mellitus
- Disease duration > 5 years
- Despite intensive insulin therapy with tight endocrinologist supervision, persistence of the following conditions : hypoglycemia unawareness (< 54 mg/dl) ; brittleness with at least two episodes of severe hypoglycemia ((defined by the need for assistance to correct the blood glucose level) or ketoacidosis per year , or often enough that the diabetologist judges the frequency to be life-threatening, the risk of transplantation and immunosuppression being judged to be less than the risk of the spontaneous course of uncontrolled diabetes
- Basal and stimulated plasma C-peptide < 0.2 ng/ml
- Creatinine clearance ≥ 50 ml/min/1.73 m2 and proteinuria < 0.5 g/24h
Key exclusion criteria (26 listed)
- Severe cardiovascular disease (recent myocardial infarction, unstable coronaropathy…)
- Severe systemic infection, including hepatitis C or B viral infection, HIV infection or tuberculosis
- Past or present neoplasia (with the exception of non melanoma skin cancers)
- Body weight > 70 kg in women and BW > 75 kg in men or BMI > 26
- Stimulated C-peptide ≥ 0.3 ng/ml upon Glucagon or Arginine stimulation
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 |
|---|---|---|
| human pancreatic islet transplantation | Procedure or surgery | – |
Primary outcome
The rate of insulin-independence, judged upon the following criteria : HbA1c < 6.1%,
post-prandial blood glucose < 180 mg/dl, mean amplitude of glycemic excursion (MAGE index)
< 60 mg/dl, basal C-peptide > 0.5 ng/ml. This insulin independent rate will be assessed 6 months
and 12 months following transplantation.
3 secondary outcomes
The rate of success according to the DiaCell composite score defined by the following 4 items : functional islet graft, defined by a basal C-peptide > 0.5 ng/ml;
good metabolic control, defined by HbA1c ≤ 6.5%; disappearance of hypoglycemic events; reduction in exogenous insulin needs ≥ 30%.
Morbidity and quality of life will also be assessed.
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 2 Mar 2012.
- Derived from this study: PubMed 26068866Lablanche S, Borot S, Wojtusciszyn A, Bayle F, Tetaz R, Badet L, Thivolet C, Morelon E, Frimat L, Penfornis A, Kessler L, Brault C, Colin C, Tauveron I, Bosco D, Berney T, Benhamou PY; GRAGIL Network. Five-Year Metabolic, Functional, and Safety Results of Patients With Type 1 Diabetes Transplanted With Allogenic Islets Within the Swiss-French GRAGIL Network. Diabetes Care. 2015 Sep;38(9):1714-22. doi: 10.2337/dc15-0094. Epub 2015 Jun 11.
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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.
Pierre Y Benhamou, MD, PhD principal investigator
Universty Hospital, Grenoble, France
Philippe Morel, MD, PhD study chair
University Hospital, Geneva, Switzerland
Charles Thivolet, MD, PhD study director
Hospices Civils de Lyon
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing human pancreatic islet transplantation in people with Type 1 Diabetes Mellitus, run by University Hospital, Grenoble at 6 sites in 2 countries.
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 5 inclusion and 26 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 2 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in France, Switzerland. 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?
The rate of insulin-independence, judged upon the following criteria : HbA1c < 6.1%,. The study lists 4 primary outcomes in all. 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 NCT00321256, 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 2 Mar 2012; AzTrials last refreshed its copy on 8 Nov 2026.