Type 1 Diabetes MellitusPhase 2NCT00468442
B-Lymphocyte Immunotherapy in Islet Transplantation
A Phase 2 study testing Allogeneic Pancreatic Islet Cells, Antithymocyte globulin and Daclizumab in people with Type 1 Diabetes Mellitus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to determine the safety and effectiveness of islet transplantation, combined with the immunosuppressive medications and medications to support… 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?
- Allogeneic Pancreatic Islet Cells, Antithymocyte globulin and Daclizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2006to Sep 2011
- Phase
- Phase 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
- Mentally stable and able to comply with study procedures
- Clinical history compatible with type 1 diabetes with onset at less than 40 years of age, insulin dependence for at least 5 years at study entry, and a sum of age and insulin dependent diabetes duration of at least 28
- Absent stimulated C-peptide (less than 0.3 ng/ml) 60 and 90 minutes post-mixed-meal tolerance test
- Involvement of intensive diabetes management, defined as:
- Self-monitoring of glucose values no less than a mean of three times each day averaged over each week
- Administration of three or more insulin injections each day or insulin pump therapy
Show all 9Show fewer
- Under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least three evaluations the 12 months prior to study enrollment
- At least one episode of severe hypoglycemia in the past 12 months, defined as an event with one of the following symptoms: memory loss; confusion; uncontrollable behavior; irrational behavior; unusual difficulty in awakening; suspected seizure; seizure; loss of consciousness; or visual symptoms in which the participant was unable to treat him/herself and which was associated with either a blood glucose (BG) level < 54 mg/dL [3.0 mmol/L] or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration, in the past 12 months prior to study enrollment
- Reduced awareness of hypoglycemia. More information about this criterion, including specific definition of hypoglycemia unawareness, is in the protocol.
Who cannot join
- Body mass index (BMI) greater than 30 kg/m2 or weight less than or equal to 50 kg
- Insulin requirement of more than 1.0 IU/kg/day or less than 15 U/day
- HbA1c greater than 10%
- Untreated proliferative diabetic retinopathy
- Systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg
- Measured glomerular filtration rate using iohexol of less than 80 ml/min/1.73m2. More information about this criterion is in the protocol.
Show all 35Show fewer
- Presence or history of macroalbuminuria (greater than 300 mg/g creatinine)
- Presence or history of panel-reactive anti-HLA antibody levels greater than 20% by flow cytometry. More information about this criterion is in the protocol.
- Pregnant, breastfeeding, or unwilling to use effective contraception throughout the study and 4 months after study completion
- Active infection, including hepatitis B, hepatitis C, HIV, or tuberculosis. More information about this criterion is in the protocol.
- Negative for Epstein-Barr virus by IgG determination
- Invasive aspergillus, histoplasmosis, or coccidioidomycosis infection within one year prior to study enrollment
- History of malignancy except for completely resected squamous or basal cell carcinoma of the skin
- Known active alcohol or substance abuse
- Baseline Hgb below the lower limits of normal, lymphopenia, neutropenia, or thrombocytopenia
- History of Factor V deficiency
- Any coagulopathy or medical condition requiring long-term anticoagulant therapy after transplantation or individuals with an INR greater than 1.5
- Severe coexisting cardiac disease, characterized by any one of the following conditions:
- Heart attack within the last 6 months
- Evidence of ischemia on functional heart exam within the year prior to study entry
- Left ventricular ejection fraction less than 30%
- Persistent elevation of liver function tests at the time of study entry
- Symptomatic cholecystolithiasis
- Acute or chronic pancreatitis
- Symptomatic peptic ulcer disease
- Severe unremitting diarrhea, vomiting, or other gastrointestinal disorders that could interfere with the ability to absorb oral medications
- Hyperlipidemia despite medical therapy (fasting LDL cholesterol greater than 130 mg/dl, treated or untreated; and/or fasting triglycerides greater than 200 mg/dl)
- Receiving treatment for a medical condition that requires chronic use of systemic steroids, except the use of 5 mg or less of prednisone daily, or an equivalent dose of hydrocortisone, for physiological replacement only
- Treatment with antidiabetic medication other than insulin within the past 4 weeks
- Use of any investigational agents within the past 4 weeks
- Received a live attenuated vaccine(s) within 2 months of study entry
- Any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial
- Treatment with any immunosuppressive regimen at the time of enrollment
- A previous islet transplant
- A previous pancreas transplant, unless the graft failed within the first week due to thrombosis, followed by pancreatectomy and transplant occurred more than 6 months prior to enrollment
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania
About this study
Official title: B-Lymphocyte Immunotherapy in Islet Transplantation: Toward Calcineurin-Inhibitor Free Immunosuppression (CIT-05)
Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to determine the safety and effectiveness of islet transplantation, combined with the immunosuppressive medications and medications to support islet survival for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.
Read the detailed description
Type 1 diabetes is commonly treated with the administration of insulin, either by multiple insulin injections or by a continuous supply of insulin through a wearable pump. Insulin therapy allows long-term survival in individuals with type 1 diabetes; however, it does not guarantee constant normal blood sugar control. Because of this, long-term type 1 diabetic survivors often develop vascular complications, such as diabetic retinopathy, an eye disease that can cause poor vision and blindness, and diabetic nephropathy, a kidney disease that can lead to kidney failure. Some individuals with type 1 diabetes develop hypoglycemia unawareness, a life-threatening condition that is not easily treatable with medication and is characterized by reduced or absent warning signals for hypoglycemia. For such individuals, pancreas or pancreatic islet transplantation are possible treatment options. Unfortunately, insulin independence among islet transplant recipients tends to decline over time. New strategies aimed at promoting engraftment of transplanted islets are needed to improve the clinical outcomes associated with this procedure. The purpose of this study is to determine the safety and efficacy of islet transplantation, when combined with an immunosuppressive medication regimen containing rituximab. This regimen is intended to treat type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes. This study will also seek to improve the understanding of determinants of success and failure of islet transplants for type 1 diabetes.
Eligible participants will be randomly assigned to this study or the Phase 3 islet transplantation study (DAIT CIT-07). Participants in this study will receive up to three separate islet transplants and a regimen of immunosuppressive medications consisting of antithymocyte globulin (ATG), sirolimus, and rituximab. They will begin receiving ATG, sirolimus, and rituximab 2 days prior to the first islet transplant. ATG will continue to be given until Day 2 post-transplant, and sirolimus will be given for the duration of the study. They will receive additional rituximab on Days 5 and 12 post-transplant.
Transplantations will involve an inpatient hospital stay and infusion of islets into the portal vein. Participants who do not achieve or maintain insulin independence by Day 75 post-transplant will be considered for a second islet transplant. Participants who remain dependent on insulin for longer than 1 month after the second transplant and who show partial graft function will be considered for a third islet transplant. Daclizumab or basiliximab will be used in place of ATG for the second and third transplants, if they are necessary. Participants who do not meet the criteria for a subsequent transplant and do not have a functioning graft will enter a reduced follow-up period.
There will be approximately 15 study visits following each transplant. A physical exam, review of adverse events, and blood collection will occur at most visits. A chest x-ray, abdominal ultrasound, electrocardiogram, quality of life questionnaires, urine collection, and glomerular filtrating rate (GFR) testing will occur at some visits. Participants will also test their own blood glucose levels at least four times per day throughout the study. A 12-month follow-up period will take place after the participant's last transplant.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Allogeneic Pancreatic Islet Cells, Antithymocyte globulin, Daclizumab, Rituximab, Sirolimus
- Keywords
- Insulin dependence, Hypoglycemia, Hypoglycemia unawareness
- 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 Pancreatic Islet CellsBiological
transplant of islet cells injected into the portal vein of the liver
Antithymocyte globulinBiological
Also called ATG
Immunosuppressive that selectively depletes activated T-cells and depletes resting T-cells in a dose-dependent manner.
DaclizumabBiological
Also called Zenapax
Will replace antithymocyte globulin in all islet transplantations after the first one
RituximabBiological
Also called Rituxan
Depletes transient B-cells
SirolimusDrug
Also called Rapamune
Maintenance immunosuppressive therapy
| Study group | Role | What they receive |
|---|---|---|
| Allogeneic Pancreatic Islet Cells | Experimental | Participants will receive up to three islet transplants and maintenance immunosuppressive therapy. Receives: Biological: Allogeneic Pancreatic Islet Cells; Biological: Antithymocyte globulin; Biological: Daclizumab; Biological: Rituximab; Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin independence
Measured: 75 days after a single islet transplant
Secondary outcomes (1)
reduction in insulin requirements, HbA1c, MAGE, LI, HYPO score, fasting glucose, beta score, quality of life
Measured: 75 days and 1 year following first and final infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2007 (estimated)
- Study startNov 2006
- Primary completionSep 2011
- Study completionSep 2011
Why it stopped: Lack of efficacy
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 National Institute of Allergy and Infectious Diseases (NIAID)The 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ali Naji, MD, PhD, Study chair, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00468442
- Sponsor's protocol ID
- DAIT CIT-05
- Status last verified
- Feb 2016
- First submitted
- 1 May 2007
- Last updated
- 21 Mar 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- B-Lymphocyte Immunotherapy in Islet Transplantation: Toward Calcineurin-Inhibitor Free Immunosuppression (CIT-05)
- ClinicalTrials.gov ID
- NCT00468442
- Acronym / sponsor ID
- DAIT CIT-05
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Insulin dependence, Hypoglycemia, Hypoglycemia unawareness
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of efficacy
- Enrolment
- 2 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Nov 2006
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 2 May 2007 (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.
Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to determine the safety and effectiveness of islet transplantation, combined with the immunosuppressive medications and medications to support islet survival for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.
Detailed description
Type 1 diabetes is commonly treated with the administration of insulin, either by multiple insulin injections or by a continuous supply of insulin through a wearable pump. Insulin therapy allows long-term survival in individuals with type 1 diabetes; however, it does not guarantee constant normal blood sugar control. Because of this, long-term type 1 diabetic survivors often develop vascular complications, such as diabetic retinopathy, an eye disease that can cause poor vision and blindness, and diabetic nephropathy, a kidney disease that can lead to kidney failure. Some individuals with type 1 diabetes develop hypoglycemia unawareness, a life-threatening condition that is not easily treatable with medication and is characterized by reduced or absent warning signals for hypoglycemia. For such individuals, pancreas or pancreatic islet transplantation are possible treatment options. Unfortunately, insulin independence among islet transplant recipients tends to decline over time. New strategies aimed at promoting engraftment of transplanted islets are needed to improve the clinical outcomes associated with this procedure. The purpose of this study is to determine the safety and efficacy of islet transplantation, when combined with an immunosuppressive medication regimen containing rituximab. This regimen is intended to treat type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes. This study will also seek to improve the understanding of determinants of success and failure of islet transplants for type 1 diabetes.
Eligible participants will be randomly assigned to this study or the Phase 3 islet transplantation study (DAIT CIT-07). Participants in this study will receive up to three separate islet transplants and a regimen of immunosuppressive medications consisting of antithymocyte globulin (ATG), sirolimus, and rituximab. They will begin receiving ATG, sirolimus, and rituximab 2 days prior to the first islet transplant. ATG will continue to be given until Day 2 post-transplant, and sirolimus will be given for the duration of the study. They will receive additional rituximab on Days 5 and 12 post-transplant.
Transplantations will involve an inpatient hospital stay and infusion of islets into the portal vein. Participants who do not achieve or maintain insulin independence by Day 75 post-transplant will be considered for a second islet transplant. Participants who remain dependent on insulin for longer than 1 month after the second transplant and who show partial graft function will be considered for a third islet transplant. Daclizumab or basiliximab will be used in place of ATG for the second and third transplants, if they are necessary. Participants who do not meet the criteria for a subsequent transplant and do not have a functioning graft will enter a reduced follow-up period.
There will be approximately 15 study visits following each transplant. A physical exam, review of adverse events, and blood collection will occur at most visits. A chest x-ray, abdominal ultrasound, electrocardiogram, quality of life questionnaires, urine collection, and glomerular filtrating rate (GFR) testing will occur at some visits. Participants will also test their own blood glucose levels at least four times per day throughout the study. A 12-month follow-up period will take place after the participant's last transplant.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allogeneic Pancreatic Islet Cells | Experimental | Biological: Allogeneic Pancreatic Islet Cells, Biological: Antithymocyte globulin, Biological: Daclizumab, Biological: Rituximab, Drug: SirolimusParticipants will receive up to three islet transplants and maintenance immunosuppressive therapy. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Mentally stable and able to comply with study procedures
- Clinical history compatible with type 1 diabetes with onset at less than 40 years of age, insulin dependence for at least 5 years at study entry, and a sum of age and insulin dependent diabetes duration of at least 28
- Absent stimulated C-peptide (less than 0.3 ng/ml) 60 and 90 minutes post-mixed-meal tolerance test
- Involvement of intensive diabetes management, defined as:
- Under the direction of an endocrinologist, diabetologist, or diabetes specialist with at least three evaluations the 12 months prior to study enrollment
Key exclusion criteria (35 listed)
- Body mass index (BMI) greater than 30 kg/m2 or weight less than or equal to 50 kg
- Insulin requirement of more than 1.0 IU/kg/day or less than 15 U/day
- HbA1c greater than 10%
- Untreated proliferative diabetic retinopathy
- Systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg
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 Pancreatic Islet Cellstransplant of islet cells injected into the portal vein of the liver | Biological | Allogeneic Pancreatic Islet Cells |
| Antithymocyte globulinAlso: ATGImmunosuppressive that selectively depletes activated T-cells and depletes resting T-cells in a dose-dependent manner. | Biological | Allogeneic Pancreatic Islet Cells |
| DaclizumabAlso: ZenapaxWill replace antithymocyte globulin in all islet transplantations after the first one | Biological | Allogeneic Pancreatic Islet Cells |
| RituximabAlso: RituxanDepletes transient B-cells | Biological | Allogeneic Pancreatic Islet Cells |
| SirolimusAlso: RapamuneMaintenance immunosuppressive therapy | Drug | Allogeneic Pancreatic Islet Cells |
Primary outcome
Insulin independence
Time frame: 75 days after a single islet transplant
1 secondary outcome
reduction in insulin requirements, HbA1c, MAGE, LI, HYPO score, fasting glucose, beta score, quality of life
Time frame: 75 days and 1 year following first and final infusion
Results and safety
The study was stopped early (reason given: Lack of efficacy). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2016.
- Click here for the Clinical Islet Transplantation Consortium Web siteLink provided by the sponsor.
- Click here for more information about the University of Pennsylvania's Type 1 Diabetes UnitLink provided by the sponsor.
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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.
Ali Naji, MD, PhD study chair
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Allogeneic Pancreatic Islet Cells, Antithymocyte globulin and Daclizumab in people with Type 1 Diabetes Mellitus, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 9 inclusion and 35 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: stopped early, as of the sponsor's last update on 21 Mar 2016. 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 phase mean?
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 was stopped early (reason given: Lack of efficacy). Results are not available in the source record.
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?
Insulin independence (time frame: 75 days after a single islet transplant). 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 21 Mar 2016.