Type 1 Diabetes MellitusPhase 1/2NITANCT00286624
Anti-Thymocyte Globulin, Cyclosporine, and RAD in Islet Transplantation
A Phase 1/2 study testing Allogeneic Islets of Langerhans, Everolimus and anti-thymocyte globulin in people with Type 1 Diabetes Mellitus and Hypoglycemia, run by University of Minnesota at 1 site in United States.
Trial summary
This study was designed to test the safety and efficacy of up to 3 pancreatic alloislet transplants in type 1 diabetic patients with hypoglycemia unawareness. 6 subjects were transplanted under this protocol using anti-thymocyte globulin induction immunosuppression and everolimus with cyclosporine maintenance… 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, Everolimus and anti-thymocyte globulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2003to Aug 2006
- 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
- Primary islet allotransplant
- Patients with type 1 diabetes mellitus under intensive insulin management
- Age 18 or older
- Ability to give written informed consent
Who cannot join
- Age less than 18 years.
- BMI >26 kg/m2.
- Insulin requirement of > 50 IU per day.
- Positive C-peptide response to intravenous arginine stimulation.
- Untreated proliferative retinopathy.
- Creatinine clearance < 60 ml/min/1.73 m2 for females and 70 ml/min/1.73 m2 for males.
Show all 30Show fewer
- Serum creatinine >1.3 mg/dl for females, >1.5 mg/dl for males.
- Previous pancreas or islet transplant.
- Presence of history of panel-reactive anti-HLA antibodies >10%.
- Positive pregnancy test, or presently breast-feeding, or failure to follow effective contraceptive measures.
- Active infection including hepatitis C, hepatitis B, HIV, or TB (or under treatment for suspected TB).
- Negative screen for Epstein-Barr Virus (EBV).
- Invasive aspergillus infection within year prior to study entry.
- History of malignancy.
- Active alcohol or substance abuse
- History of non-adherence to prescribed regimens.
- Psychiatric disorder making the subject not a suitable candidate for transplantation.
- Inability to provide informed consent.
- Baseline Hgb < 11.7 g/dl in females, or < 13 g/dl in males; lymphopenia (<1,000/microL), or leukopenia (<3,000 total leukocytes/microL), or an absolute CD4+ count <500/microL., or platelets <150,000/microL
- History of coagulopathy or medical condition requiring long-term anticoagulant therapy after transplantation or patient with INR >1.5.
- Severe co-existing cardiac disease.
- Baseline liver function tests outside of normal range or history of significant liver disease.
- Active peptic ulcer disease.
- Severe unremitting diarrhea or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications.
- Presence of severe allergy requiring acute or chronic treatment, or hypersensitivity to drugs similar to RAD (e.g., macrolides).
- Known hypersensitivity to rabbit proteins.
- Hyperlipidemia (fasting LDL cholesterol > 130 mg/dl, treated or untreated; and/or fasting triglycerides > 200 mg/dl).
- Addison's disease.
- Under treatment requiring chronic use of systemic steroids.
- 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: A One-Year, Single-Center, Prospective, Open-Label Study of the Safety, Tolerability, and Preliminary Efficacy of Anti-Thymocyte Globulin, Cyclosporine, and RAD in Type 1 Diabetic Islet Transplant Recipients
This study was designed to test the safety and efficacy of up to 3 pancreatic alloislet transplants in type 1 diabetic patients with hypoglycemia unawareness. 6 subjects were transplanted under this protocol using anti-thymocyte globulin induction immunosuppression and everolimus with cyclosporine maintenance immunosuppression.
Read the detailed description
This is a Phase I/II study designed to assess the safety and efficacy of sequential islet allotransplantation for the reestablishment of stable glycemic control in type 1 diabetic recipients. A total of 6 patients with type 1 diabetes have received up to three transplants of islets from different donor pancreases.
Potential candidates for islet allotransplantation included patients age 18 and older with type 1 diabetes. Induction immunotherapy for the first transplant consisted of anti-thymocyte globulin; basiliximab was used for any subsequent transplants. Peritransplant anti-inflammatory treatment with etanercept was given for each islet transplant. Maintenance immunosuppression is with cyclosporine and RAD. It is felt that those patients in whom metabolic lability/instability, reduced awareness of hypoglycemia, poor glycemic control, and progressive secondary complications persist despite continued and intensive efforts made in close cooperation with their diabetes care team are particularly likely to have a favorable benefit/risk ratio.
Adverse events, irrespective of their presumed relationship to the transplantation of allogeneic islets and/or protocol-regulated treatment products (concomitant therapy), are being monitored and recorded throughout the first year after the final islet transplant.
The proportion of single and sequential donor islet allograft recipients with full (insulin independence and HbA1c <7%) and partial (insulin dependence, basal or arginine-stimulated C-peptide levels of greater or equal to 0.5 ng/mL and HbA1c <7%) islet graft function at one year after the final islet transplant will be assessed. The impact of islet transplantation on quality of life will also be assessed.
The predictive value for posttransplant insulin independence of factors such as insulin resistance before and at intervals after pancreatectomy, cellular composition of the transplant, number of beta cells transplanted; and viability and insulin secretory response of isolated islets are being assessed.
- Conditions
- Type 1 Diabetes Mellitus, Hypoglycemia
- Being tested
- Allogeneic Islets of Langerhans, Everolimus, anti-thymocyte globulin, Cyclosporine
- 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
Also called Islets
Up to 3 intraportal infusions of cadaveric pancreatic islets of Langerhans. First infusion to contain at least 5,000 islet equivalents/kg body weight. Subsequent infusions to contain at least 3,000 islet equivalents/kg body weight.
EverolimusDrug
Also called RAD
Loading dose of 3 mg PO on day -2 relative to transplant, followed at least 12 hours later by dose of 1.5 mg PO BID. The daily dose will be adjusted according to the whole blood 12-hr trough to target 3-15 ng/ml for the first 3 months and 3-12 ng/ml thereafter.
anti-thymocyte globulinDrug
Also called ATG, Thymogloblin
A total of 6 mg/kg IV over 12 hours on days -2, -1, 0, +1, and +2. The dose will be 0.5 mg/kg on day -2, 1.0 mg/kg on day -1, and 1.5 mg/kg on days 0, +1, and +2.
CyclosporineDrug
Also called Neoral
Cyclosporine started on day +1 relative to the first islet transplant. Initial dose of 3 mg/kg/day administered in 2 divided doses; then adjusted to maintain target levels of 400 (350-500) ng/mL for the first three months following islet transplant and 300 (200-350) ng/mL thereafter.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Allogeneic islet transplantation with anti-thymocyte globulin induction and cyclosporine and RAD maintenance immunosuppression Receives: Biological: Allogeneic Islets of Langerhans; Drug: Everolimus; Drug: anti-thymocyte globulin; Drug: Cyclosporine |
What is being measured
The primary outcome is the main question the study is designed to answer.
• The incidence, timing, and severity of adverse events during one year after the first and any subsequent islet transplants.
Measured: 1 year
• Incidence and severity of hypoglycemia during the first year after the first and any subsequent islet transplants.
Measured: 1 yr
• The proportion of recipients who develop alloantibodies directed at islet donor alloantigens during the first year after the first and any subsequent islet transplants.
Measured: 1 year
Secondary outcomes (5)
• The proportion of subjects who achieve insulin independence in the first year after single-donor or sequential transplantation.
Measured: 1 year
• The proportion of islet allograft recipients with full and partial islet graft function at one year after the most recent islet transplant.
Measured: 1 year
• Glycemic control and insulin secretory responses during the first year after the first and any subsequent transplants.
Measured: 1 year
• The effect of donor age, pretransplant islet insulin secretory response in vitro, number of transplanted islet equivalents (IEQ), number of transplanted beta cells, pretransplant recipient insulin requirements and action, recipient body mass index (BM
Measured: Day of transplant
• The impact of islet transplantation on the quality of life of transplant recipients.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2006 (estimated)
- Study startMar 2003
- Primary completionAug 2006
- Study completionAug 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation, National Institutes of Health (NIH), Novartis
- Investigators
- Bernhard J. Hering, M.D., Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00286624
- Sponsor's protocol ID
- 0207M29841
- Acronym
- NITA
- Status last verified
- May 2008
- First submitted
- 2 Feb 2006
- Last updated
- 8 May 2008
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A One-Year, Single-Center, Prospective, Open-Label Study of the Safety, Tolerability, and Preliminary Efficacy of Anti-Thymocyte Globulin, Cyclosporine, and RAD in Type 1 Diabetic Islet Transplant Recipients
- ClinicalTrials.gov ID
- NCT00286624
- Acronym / sponsor ID
- NITA / 0207M29841
- Conditions
- Type 1 Diabetes Mellitus, Hypoglycemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation, National Institutes of Health (NIH), Novartis
- Study start
- Mar 2003
- Primary completion
- Aug 2006 (actual)
- Study completion
- Aug 2006 (actual)
- First posted
- 3 Feb 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 study was designed to test the safety and efficacy of up to 3 pancreatic alloislet transplants in type 1 diabetic patients with hypoglycemia unawareness. 6 subjects were transplanted under this protocol using anti-thymocyte globulin induction immunosuppression and everolimus with cyclosporine maintenance immunosuppression.
Detailed description
This is a Phase I/II study designed to assess the safety and efficacy of sequential islet allotransplantation for the reestablishment of stable glycemic control in type 1 diabetic recipients. A total of 6 patients with type 1 diabetes have received up to three transplants of islets from different donor pancreases.
Potential candidates for islet allotransplantation included patients age 18 and older with type 1 diabetes. Induction immunotherapy for the first transplant consisted of anti-thymocyte globulin; basiliximab was used for any subsequent transplants. Peritransplant anti-inflammatory treatment with etanercept was given for each islet transplant. Maintenance immunosuppression is with cyclosporine and RAD. It is felt that those patients in whom metabolic lability/instability, reduced awareness of hypoglycemia, poor glycemic control, and progressive secondary complications persist despite continued and intensive efforts made in close cooperation with their diabetes care team are particularly likely to have a favorable benefit/risk ratio.
Adverse events, irrespective of their presumed relationship to the transplantation of allogeneic islets and/or protocol-regulated treatment products (concomitant therapy), are being monitored and recorded throughout the first year after the final islet transplant.
The proportion of single and sequential donor islet allograft recipients with full (insulin independence and HbA1c <7%) and partial (insulin dependence, basal or arginine-stimulated C-peptide levels of greater or equal to 0.5 ng/mL and HbA1c <7%) islet graft function at one year after the final islet transplant will be assessed. The impact of islet transplantation on quality of life will also be assessed.
The predictive value for posttransplant insulin independence of factors such as insulin resistance before and at intervals after pancreatectomy, cellular composition of the transplant, number of beta cells transplanted; and viability and insulin secretory response of isolated islets are being assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: Allogeneic Islets of Langerhans, Drug: Everolimus, Drug: anti-thymocyte globulin, Drug: CyclosporineAllogeneic islet transplantation with anti-thymocyte globulin induction and cyclosporine and RAD maintenance immunosuppression |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Primary islet allotransplant
- Patients with type 1 diabetes mellitus under intensive insulin management
- Age 18 or older
- Ability to give written informed consent
Key exclusion criteria (30 listed)
- Age less than 18 years.
- BMI >26 kg/m2.
- Insulin requirement of > 50 IU per day.
- Positive C-peptide response to intravenous arginine stimulation.
- Untreated proliferative 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 LangerhansAlso: IsletsUp to 3 intraportal infusions of cadaveric pancreatic islets of Langerhans. First infusion to contain at least 5,000 islet equivalents/kg body weight. Subsequent infusions to contain at least 3,000 islet equivalents/kg body weight. | Biological | 1 |
| EverolimusAlso: RADLoading dose of 3 mg PO on day -2 relative to transplant, followed at least 12 hours later by dose of 1.5 mg PO BID. The daily dose will be adjusted according to the whole blood 12-hr trough to target 3-15 ng/ml for the first 3 months and 3-12 ng/ml thereafter. | Drug | 1 |
| anti-thymocyte globulinAlso: ATG, ThymogloblinA total of 6 mg/kg IV over 12 hours on days -2, -1, 0, +1, and +2. The dose will be 0.5 mg/kg on day -2, 1.0 mg/kg on day -1, and 1.5 mg/kg on days 0, +1, and +2. | Drug | 1 |
| CyclosporineAlso: NeoralCyclosporine started on day +1 relative to the first islet transplant. Initial dose of 3 mg/kg/day administered in 2 divided doses; then adjusted to maintain target levels of 400 (350-500) ng/mL for the first three months following islet transplant and 300 (200-350) ng/mL thereafter. | Drug | 1 |
Primary outcome
• The incidence, timing, and severity of adverse events during one year after the first and any subsequent islet transplants.
Time frame: 1 year
• Incidence and severity of hypoglycemia during the first year after the first and any subsequent islet transplants.
Time frame: 1 yr
• The proportion of recipients who develop alloantibodies directed at islet donor alloantigens during the first year after the first and any subsequent islet transplants.
Time frame: 1 year
5 secondary outcomes
• The proportion of subjects who achieve insulin independence in the first year after single-donor or sequential transplantation.
Time frame: 1 year
• The proportion of islet allograft recipients with full and partial islet graft function at one year after the most recent islet transplant.
Time frame: 1 year
• Glycemic control and insulin secretory responses during the first year after the first and any subsequent transplants.
Time frame: 1 year
• The effect of donor age, pretransplant islet insulin secretory response in vitro, number of transplanted islet equivalents (IEQ), number of transplanted beta cells, pretransplant recipient insulin requirements and action, recipient body mass index (BM
Time frame: Day of transplant
• The impact of islet transplantation on the quality of life of transplant recipients.
Time frame: 1 year
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 8 May 2008.
- Diabetes Institute for Immunology and Transplantation - U of MLink provided by the sponsor.
Related trials for Type 1 Diabetes Mellitus
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 2
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Metastatic Colorectal Cancer
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
Continuous Glucose Monitoring, Type 1 Diabetes
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
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, Everolimus and anti-thymocyte globulin 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 4 inclusion and 30 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 8 May 2008. 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?
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 incidence, timing, and severity of adverse events during one year after the first and any subsequent islet transplants. (time frame: 1 year). The study lists 3 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 8 May 2008.