Type 1 Diabetes MellitusPhase 1/2NCT00265473
MGA031, Sirolimus and Tacrolimus in Islet Transplantation
A Phase 1/2 study testing Allogeneic Islets of Langerhans in people with Type 1 Diabetes Mellitus and Hypoglycemia, run by University of Minnesota at 1 site in United States.
Trial summary
This clinical trial is designed to extend the observations made in our pilot clinical trial (IND 8971, Study #1) on the safety and efficacy of immunotherapy with the anti-CD3 monoclonal antibody hOKT3γ1 (Ala-Ala), (currently called MGA031) combined with sirolimus and tacrolimus in preventing rejection and autoimmune… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 1 Diabetes Mellitus, Hypoglycemia
- What is being tested?
- Allogeneic Islets of Langerhans
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2005to Jun 2010
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Age 18 to 65 years of age.
- Ability to provide written informed consent.
- Mentally stable and able to comply with the procedures of the study.
- Clinical history compatible with type 1 diabetes with onset of disease at <40 years of age and insulin-dependence for > 5 years at the time of enrollment.
- Absent stimulated C-peptide (<0.3ng/ml) in response to a mixed meal tolerance test.
- Involvement in intensive diabetes management defined as self monitoring of glucose values no less than a mean of three times each day averaged over each week and by the administration of three or more insulin injections each day or insulin pump therapy. Such management must be under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least 3 clinical evaluations during the previous 12 months.
- At least one episode of severe hypoglycemia in the past 3 years defined as an event with symptoms compatible with hypoglycemia in which the subject required the assistance of another person and which was associated with either a blood glucose level < 50 mg/dl or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration).
- Reduced awareness of hypoglycemia.
Who cannot join
- Any previous transplant.
- BMI >27 kg/m2 or patient weight ≤ 50kg.
- Insulin requirement of > 0.8 IU/kg/day or 50 IU/day.
- HbA1c >10%.
- Untreated proliferative diabetic retinopathy.
- Uncontrolled Hypertension.
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- Estimated glomerular filtration rate <70 ml/min/1.73 m2 for females and <80 ml/min/1.73 m2 for males
- Presence or history of macroalbuminuria (>300mg/d).
- Presence or history of panel-reactive anti-HLA antibodies >20% by flow cytometry.
- Females: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 3 months after discontinuation. Males: intent to procreate during the duration of the study or within 3 months after discontinuation or unwillingness to use effective measures of contraception.
- Active infection.
- Negative screen for Epstein-Barr Virus (EBV).
- Invasive aspergillus infection within one year prior to study entry.
- Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin.
- Active alcohol, tobacco or substance abuse.
- Baseline Hgb below the lower limits of normal at the local laboratory; lymphopenia, neutropenia, or thrombocytopenia.
- A history of Factor V deficiency.
- Any coagulopathy or medical condition requiring long-term anticoagulant therapy.
- Severe co-existing cardiac disease.
- Persistent elevation of liver function tests.
- Symptomatic cholecystolithiasis.
- Acute or chronic pancreatitis.
- Symptomatic peptic ulcer disease.
- Unremitting diarrhea, vomiting or other gastrointestinal disorders potentially interfering with absorption.
- Hyperlipidemia despite medical therapy (fasting LDL cholesterol > 130 mg/dl, treated or untreated; and/or fasting triglycerides > 200 mg/dl).
- Chronic use of systemic steroids.
- Use of any other investigational agents within 4 weeks of participation.
- Administration of live attenuated vaccine(s) within 2 months of enrollment.
- Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: hOKT3γ1 (Ala-Ala), Sirolimus and Low Dose Tacrolimus Therapy in Type 1 Diabetic Islet Allograft Recipients
This clinical trial is designed to extend the observations made in our pilot clinical trial (IND 8971, Study #1) on the safety and efficacy of immunotherapy with the anti-CD3 monoclonal antibody hOKT3γ1 (Ala-Ala), (currently called MGA031) combined with sirolimus and tacrolimus in preventing rejection and autoimmune destruction of deceased donor pancreatic islet transplants in type 1 diabetic recipients.
Read the detailed description
Type 1 diabetes mellitus continues to be a therapeutic challenge. Previous studies have shown that failure to prevent hypoglycemia and hyperglycemia results in acute and chronic complications, leading to poor quality of life, premature death, and considerable health care costs in 30% to 50% of diabetic patients. Therefore, establishing safe and effective ways to achieve and maintain normoglycemia would have substantial implications for the well-being of individuals with diabetes. Intensive insulin therapy has been shown to reduce the risk of chronic complications in patients who achieve near-normalization of glycemia. However, such therapy is labor-intensive, difficult to implement for many patients, and limited by the accompanying increased frequency of severe hypoglycemia. Currently, the only way to restore and sustain normoglycemia without the associated risk of hypoglycemia is by replacing the patient's islets of Langerhans, either by transplanting a vascularized pancreas or, much less invasively, by infusing isolated islets.
Strategies that selectively inactivate autoreactive T cells and prevent allorejection of transplanted islets in the absence of diabetogenic side effects need to be developed for islet transplants to survive in autoimmune diabetic recipients. The current clinical study will extend the observations made in our first pilot clinical trial (IND 8971, Study #1) that provided preliminary information on the safety and efficacy of immunotherapy with the anti-CD3 monoclonal antibody hOKT3γ1 (Ala-Ala), (currently called MGA031) combined with sirolimus and tacrolimus in preventing rejection and autoimmune destruction of deceased donor pancreatic islet transplants in type 1 diabetic recipients.
In the pilot study 4 of 6 single islet transplant recipients remained insulin independent with normal HbA1c and no episodes of hypoglycemia throughout the 1 year post-transplant period. Three of those four participants have maintained insulin independence for > 3.5, >4.5 and >5 years post islet transplant. These preliminary findings warrant an extension study involving more recipients and more comprehensive immunologic monitoring to examine in greater detail the impact of MGA031 induction immunotherapy on T cell responses operative in rejection and autoimmune destruction of transplanted islets as well as on formation of regulatory T cell function for the protection of transplanted islets.
A total of 5 patients with type 1 diabetes will be transplanted under this protocol. Islet transplant recipients will be admitted for 5 days and followed for one year after transplantation.
- Conditions
- Type 1 Diabetes Mellitus, Hypoglycemia
- Being tested
- Allogeneic Islets of Langerhans
- 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.
Allogeneic Islets of LangerhansBiological
Intraportal infusion of islets of Langerhans
| Study group | Role | What they receive |
|---|---|---|
| Allogeneic Islets of Langerhans | Experimental | Islet infusion Receives: Biological: Allogeneic Islets of Langerhans |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subjects With Full Islet Function.
Proportion of subjects with full islet function (i.e. insulin independent) at one year after initial islet transplant.
Measured: At one year after initial transplant.
Serious Adverse Events Related to Immunosuppressive Therapy.
Number of serious adverse events related to immunosuppressive therapy.
Measured: Day 0 - Day 365
Secondary outcomes (3)
Subjects With Partial Islet Function and no Episodes of Severe Hypoglycemia;
Proportion of subjects with partial islet function and no episodes of severe hypoglycemia at one year after initial islet transplant.
Measured: At one year after initial transplant
Insulin Independent Single-donor Subjects.
Proportion of insulin independent single-donor subjects at day 75 after transplant
Measured: At 75 days after transplant
Insulin Independent Multiple-donor Subjects.
Proportion of insulin independent multiple-donor subjects at one year after final transplant. Participant received more than one islet transplant.
Measured: At one year after final transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2005 (estimated)
- Study startNov 2005
- Primary completionMay 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe 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
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), Juvenile Diabetes Research Foundation
- Responsible party
- Sponsor
- Investigators
- Bernhard J. Hering, M.D., Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00265473
- Sponsor's protocol ID
- 0407M62505
- Status last verified
- Jan 2017
- First submitted
- 12 Dec 2005
- Last updated
- 9 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- hOKT3γ1 (Ala-Ala), Sirolimus and Low Dose Tacrolimus Therapy in Type 1 Diabetic Islet Allograft Recipients
- ClinicalTrials.gov ID
- NCT00265473
- Acronym / sponsor ID
- 0407M62505
- Conditions
- Type 1 Diabetes Mellitus, Hypoglycemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), Juvenile Diabetes Research Foundation
- Study start
- Nov 2005
- Primary completion
- May 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 14 Dec 2005 (estimated)
- Results
- Posted 21 Sep 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial is designed to extend the observations made in our pilot clinical trial (IND 8971, Study #1) on the safety and efficacy of immunotherapy with the anti-CD3 monoclonal antibody hOKT3γ1 (Ala-Ala), (currently called MGA031) combined with sirolimus and tacrolimus in preventing rejection and autoimmune destruction of deceased donor pancreatic islet transplants in type 1 diabetic recipients.
Detailed description
Type 1 diabetes mellitus continues to be a therapeutic challenge. Previous studies have shown that failure to prevent hypoglycemia and hyperglycemia results in acute and chronic complications, leading to poor quality of life, premature death, and considerable health care costs in 30% to 50% of diabetic patients. Therefore, establishing safe and effective ways to achieve and maintain normoglycemia would have substantial implications for the well-being of individuals with diabetes. Intensive insulin therapy has been shown to reduce the risk of chronic complications in patients who achieve near-normalization of glycemia. However, such therapy is labor-intensive, difficult to implement for many patients, and limited by the accompanying increased frequency of severe hypoglycemia. Currently, the only way to restore and sustain normoglycemia without the associated risk of hypoglycemia is by replacing the patient's islets of Langerhans, either by transplanting a vascularized pancreas or, much less invasively, by infusing isolated islets.
Strategies that selectively inactivate autoreactive T cells and prevent allorejection of transplanted islets in the absence of diabetogenic side effects need to be developed for islet transplants to survive in autoimmune diabetic recipients. The current clinical study will extend the observations made in our first pilot clinical trial (IND 8971, Study #1) that provided preliminary information on the safety and efficacy of immunotherapy with the anti-CD3 monoclonal antibody hOKT3γ1 (Ala-Ala), (currently called MGA031) combined with sirolimus and tacrolimus in preventing rejection and autoimmune destruction of deceased donor pancreatic islet transplants in type 1 diabetic recipients.
In the pilot study 4 of 6 single islet transplant recipients remained insulin independent with normal HbA1c and no episodes of hypoglycemia throughout the 1 year post-transplant period. Three of those four participants have maintained insulin independence for > 3.5, >4.5 and >5 years post islet transplant. These preliminary findings warrant an extension study involving more recipients and more comprehensive immunologic monitoring to examine in greater detail the impact of MGA031 induction immunotherapy on T cell responses operative in rejection and autoimmune destruction of transplanted islets as well as on formation of regulatory T cell function for the protection of transplanted islets.
A total of 5 patients with type 1 diabetes will be transplanted under this protocol. Islet transplant recipients will be admitted for 5 days and followed for one year after transplantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allogeneic Islets of Langerhans | Experimental | Biological: Allogeneic Islets of LangerhansIslet infusion |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18 to 65 years of age.
- Ability to provide written informed consent.
- Mentally stable and able to comply with the procedures of the study.
- Clinical history compatible with type 1 diabetes with onset of disease at <40 years of age and insulin-dependence for > 5 years at the time of enrollment.
- Absent stimulated C-peptide (<0.3ng/ml) in response to a mixed meal tolerance test.
Key exclusion criteria (29 listed)
- Any previous transplant.
- BMI >27 kg/m2 or patient weight ≤ 50kg.
- Insulin requirement of > 0.8 IU/kg/day or 50 IU/day.
- HbA1c >10%.
- Untreated proliferative diabetic retinopathy.
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 |
|---|---|---|
| Allogeneic Islets of LangerhansIntraportal infusion of islets of Langerhans | Biological | Allogeneic Islets of Langerhans |
Primary outcome
Subjects With Full Islet Function.
Time frame: At one year after initial transplant.
Proportion of subjects with full islet function (i.e. insulin independent) at one year after initial islet transplant.
Serious Adverse Events Related to Immunosuppressive Therapy.
Time frame: Day 0 - Day 365
Number of serious adverse events related to immunosuppressive therapy.
3 secondary outcomes
Subjects With Partial Islet Function and no Episodes of Severe Hypoglycemia;
Time frame: At one year after initial transplant
Insulin Independent Single-donor Subjects.
Time frame: At 75 days after transplant
Insulin Independent Multiple-donor Subjects.
Time frame: At one year after final transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Bernhard J. Hering, M.D. principal investigator
University of Minnesota
1 site 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 Allogeneic Islets of Langerhans in people with Type 1 Diabetes Mellitus and Hypoglycemia, run by University of Minnesota at 1 site in United States.
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 8 inclusion and 29 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 9 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Yes. Results are posted in the registry (first posted 21 Sep 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Subjects With Full Islet Function. (time frame: At one year after initial transplant.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Mar 2017.