A Phase 2 interventional study of Islet Transplantation and Sirolimus in Diabetes Mellitus, Insulin-Dependent, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 9 sites in 5 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2017-03-15.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 2, Interventional, and Treatment
The purpose of this study is to test whether the islet cell transplantation procedures and results from a previous study in Edmonton, Canada, can be repeated. The study also is designed to learn more about diabetes control using islet cell transplantation.
This is a Phase I/II study (a study that examines effectiveness and looks for side effects). The transplanting of islet cells has been studied in Type 1 diabetic patients whose blood sugar levels will not stay normal, despite intensive insulin therapy. A recent study conducted in Edmonton, Canada, was able to demonstrate that islet transplantation led to insulin independence in a majority of the patients treated. This study extends the results obtained from the Edmonton study, which used islet transplantation in Type 1 diabetic patients with steroid-free immunosuppression.
This is a Phase I/II study (a study that examines effectiveness and looks for side effects). The transplanting of islet cells has been studied in Type 1 diabetic patients whose blood sugar levels will not stay normal, despite intensive insulin therapy. A recent study conducted in Edmonton, Canada, was able to demonstrate that islet transplantation led to insulin independence in a majority of the patients treated. This study extends the results obtained from the Edmonton study, which used islet transplantation in Type 1 diabetic patients with steroid-free immunosuppression.
Eligible patients were randomly selected from the total pool of people who applied through the Immune Tolerance Network. Patients will receive at least 10,000 "islet equivalents" per kilogram (2.2 pounds) of body weight. This likely will require 2 separate islet infusions from 2 separate donors. Immediately before the first transplant, patients will be given anti-rejection (immune suppressing) drugs, including tacrolimus and sirolimus (orally) and daclizumab (intravenously). The islets will be infused into the liver through a tube placed in the portal vein. Heparin (a medication to prevent blood clots) will be administered with the islet infusion. A longer-acting form of heparin will also be given by daily injections during the next week after each transplant. After surgery, patients will receive insulin intravenously for 24 hours. Patients will have an abdominal ultrasound and blood tests to determine liver function. If fewer than 10,000 islets were transplanted, patients will continue insulin treatment, with the dosages adjusted if necessary to account for the transplanted islets. They will take daclizumab every 2 weeks for 8 weeks and tacrolimus and sirolimus daily. Patients will be given antibiotics to prevent infections. Blood tests to determine how much immunosuppressant drug is in the blood will be performed until the drug is at a stable level. Periodically there will be tests to see if the islet cells are functioning. Blood will be drawn to check drug levels and for other tests routinely. Daily insulin requirements will be checked, and these will be recorded monthly. Patients will be followed for at least 1 year post last islet transplantation. Additional follow-up may be provided at least annually for up to 9 years post first transplantation.
3,522 studies on the registry are indexed under Diabetes Mellitus, Type 1; 577 are open to participants now.
This study's enrollment of 36 is close to the median of 40 across 2,649 interventional studies indexed under Diabetes Mellitus, Type 1.
Browse Diabetes Mellitus, Type 1 studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,401 studies on the registry; 179 are open to participants now.
Of its 396 completed or terminated interventional studies of FDA-regulated products, 294 (74%) have results posted.
Counted across the registry records on this site, refreshed daily.
Patients may be eligible for this study if they:
Exclusion Criteria
Patients will not be eligible for this study if they:
All study participants
Procedure: Islet Transplantation · Drug: Sirolimus · Drug: Tacrolimus · Drug: Daclizumab · Drug: Sulfamethoxazole · Drug: Ganciclovir · Drug: Trimethoprim · Drug: Pentamidine
Participants will receive portal vein islet infusions (up to 3), e.g., islet transplantations, with a targeted total of exceeding 10,000 islet equivalents per kilogram of body weight (IE/kg) per infusion. Up to three transplants are possible depending on individual results.
Administered at a dose of 0.2 mg/kg by mouth once pre-transplantation then 0.1 mg/kg daily post-transplantation. Dosing will be adjusted to achieve a trough peripheral blood level of 12-15 ng/mL x3 months after transplantation and 7-12 ng/mL for the remainder of the study.
Administered at a dose of 1 mg by mouth once pre-transplantation followed by 1 mg twice daily post transplantation. Levels will be adjusted to achieve a peripheral blood trough level of 3-6 ng/mL for maintenance immunosuppression.
Administered at a dose of 1 mg/kg intravenously immediately pre-transplantation and 2, 4, 6, and 8 weeks post-transplantation, totaling 5 doses(over 8 weeks). Further daclizumab dosing may be necessary based on individual results and islet transplantation needs.
An antibacterial used to prevent opportunistic infections
An antiviral used to kill viruses and stop viral replication
An antibacterial used to prevent opportunistic infections
An antiprotozoal used to prevent disease
Percent of Participants That Achieved Insulin Independence With Adequate Control of Blood Glucose Levels at One Year Post Final Islet Transplantation.
Insulin independence: exogenous insulin not required and glycemic control is achieved as defined by maintaining 1.) a blood glycosylated hemoglobin (HbA1c) level \< 6.5% (Normal:\<5.7%; pre-diabetes: 5.7% -6.4%; diabetes: 6.5% or higher),2) a blood glucose level after an overnight fast not exceeding 140 mg per deciliter (dL) more than three times in any week (Normal: 70 to 120 mg/dL), and 3)not exceeding a 2-hour postprandial blood glucose level of 180 mg/dL more than four times per week (Normal: \<140mg/dL if \<=50 years of age, \<150 mg/dL for ages 50-60 years and \<160 mg/dL for ages 60+)
Time frame: One year status post participant receipt of final islet transplantation
Percent of Participants With Partial Islet Function One Year Post Final Islet Transplantation.
Partial islet function definition: a fasting basal C-peptide level \>= 0.3 ng/mL and a continuing need for insulin or suboptimal glycemic control (Note: C-peptide is a substance that the pancreas releases into the bloodstream in equal amounts to insulin, thereby showing how much insulin the body is making). Adequate glycemic control is defined by: 1) a blood HbA1c level \<6.5%, 2) a blood glucose level after an overnight fast not exceeding 140 mg/dL more than three times in any week and, 3) a 2-hour postprandial blood glucose level not exceeding 180 mg/dL more than four times per week
Time frame: One year post receipt of final islet transplantation
Percent of Participants That Achieved Insulin Independence From First Transplant
Insulin independence: exogenous insulin not required and glycemic control is achieved as defined by maintaining 1) a blood glycosylated hemoglobin (HbA1c) level \< 6.5% (Normal:\<5.7%; pre-diabetes: 5.7% -6.4%; diabetes: 6.5% or higher),2) a blood glucose level after an overnight fast not exceeding 140 mg per deciliter (dL) more than three times in any week (Normal: 70 to 120 mg/dL), and 3)not exceeding a 2-hour postprandial blood glucose level of 180 mg/dL more than four times per week (Normal: \<140mg/dL if \<=50 years of age, \<150 mg/dL for ages 50-60 years and \<160 mg/dL for ages 60+)
Time frame: First transplantation until end of study (up to six years post final transplantation)
Percent of Participants With Detectable Fasting Basal C-Peptide Levels
C-peptide is a substance that the pancreas releases into the bloodstream in equal amounts to insulin, thereby showing how much insulin the body is making. C-peptide secretion is used to measure the function of transplanted islets. Higher levels indicate better islet function. Detectable fasting basal levels of C-peptide secretion are \>=0.3 ng/ml.
Time frame: Two years post first transplantation
Nine centers recruited participants 18 to 65 years of age who had Type 1 diabetes mellitus for more than five years, recurrent neuroglycopenia that included reduced awareness of their hypoglycemic episodes or severe glycemic lability, and fulfilled all eligibility criteria. Refer to the Eligibility section for more details.
| Milestone | Islet Transplantation |
|---|---|
| Started | 36 |
| Completed | 25 |
| Not completed | 11 |
| Withdrew: Adverse event | 1 |
| Withdrew: Lost to follow-up | 1 |
| Withdrew: Withdrawal by subject | 6 |
| Withdrew: Unknown reasons | 2 |
| Withdrew: Immunosuppression-related side effects | 1 |
Insulin independence: exogenous insulin not required and glycemic control is achieved as defined by maintaining 1.) a blood glycosylated hemoglobin (HbA1c) level \< 6.5% (Normal:\<5.7%; pre-diabetes: 5.7% -6.4%; diabetes: 6.5% or higher),2) a blood glucose level after an overnight fast not exceeding 140 mg per deciliter (dL) more than three times in any week (Normal: 70 to 120 mg/dL), and 3)not exceeding a 2-hour postprandial blood glucose level of 180 mg/dL more than four times per week (Normal: \<140mg/dL if \<=50 years of age, \<150 mg/dL for ages 50-60 years and \<160 mg/dL for ages 60+)
| Percent of Participants | Islet Transplantation |
|---|---|
| Insulin Independence at One Year | 44 |
| Insulin Independence with One Transplant | 14 |
| Insulin Independence with Two Transplants | 17 |
| Insulin Independence with Three Transplants | 14 |
Partial islet function definition: a fasting basal C-peptide level \>= 0.3 ng/mL and a continuing need for insulin or suboptimal glycemic control (Note: C-peptide is a substance that the pancreas releases into the bloodstream in equal amounts to insulin, thereby showing how much insulin the body is making). Adequate glycemic control is defined by: 1) a blood HbA1c level \<6.5%, 2) a blood glucose level after an overnight fast not exceeding 140 mg/dL more than three times in any week and, 3) a 2-hour postprandial blood glucose level not exceeding 180 mg/dL more than four times per week
| Percent of Participants | Islet Transplantation |
|---|---|
| Percent of Participants With Partial Islet Function One Year Post Final Islet Transplantation. | 28 |
Insulin independence: exogenous insulin not required and glycemic control is achieved as defined by maintaining 1) a blood glycosylated hemoglobin (HbA1c) level \< 6.5% (Normal:\<5.7%; pre-diabetes: 5.7% -6.4%; diabetes: 6.5% or higher),2) a blood glucose level after an overnight fast not exceeding 140 mg per deciliter (dL) more than three times in any week (Normal: 70 to 120 mg/dL), and 3)not exceeding a 2-hour postprandial blood glucose level of 180 mg/dL more than four times per week (Normal: \<140mg/dL if \<=50 years of age, \<150 mg/dL for ages 50-60 years and \<160 mg/dL for ages 60+)
| Percent of Participants | Islet Transplantation |
|---|---|
| Percent of Participants That Achieved Insulin Independence From First Transplant | 58 |
C-peptide is a substance that the pancreas releases into the bloodstream in equal amounts to insulin, thereby showing how much insulin the body is making. C-peptide secretion is used to measure the function of transplanted islets. Higher levels indicate better islet function. Detectable fasting basal levels of C-peptide secretion are \>=0.3 ng/ml.
| Percent of Participants | Islet Transplantation |
|---|---|
| Percent of Participants With Detectable Fasting Basal C-Peptide Levels | 70 |
Seven participants from US sites were included in the extended follow-up. These participants were monitored yearly from year three post last transplantation (the original end of study follow-up) through August 30, 2010 (up to 9 years post first transplantation), at which point they were transferred to a new protocol (ITN040CT \[NCT01309022\]). Glycosylated hemoglobin (HbA1c) is a measure of the average plasma glucose concentration over prolonged periods of time. (Normal:\<5.7%; pre-diabetes: 5.7% -6.4%; diabetes: 6.5% or higher)
| HbA1c Percentage | Islet Transplantation |
|---|---|
| HbA1c Plasma Laboratory Values for Participants in the Extended Follow-up Study Phase | 6.2 (6.0 to 6.5) |
Seven participants from US sites were included in the extended follow-up. These participants were monitored yearly from year three post last transplantation (the original end of study follow-up) through August 30, 2010 (up to 9 years post first transplantation), at which point they were transferred to a new protocol (ITN040CT \[NCT01309022\]). Serum creatinine is a measure of renal function. Normal ranges are from 0.5 to 1.0 mg/dL for females and 0.7 to 1.2 mg/dL for males.
| mg/dL | Islet Transplantation |
|---|---|
| Serum Creatinine Levels for Participants in the Extended Follow-up Study Phase | 0.9 (0.7 to 1.6) |
Collected over First transplant until end of study (up to 9 years post first transplant). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Islet Transplantation | — | 17/36 (47.2%) | 36/36 (100%) |
| Event | Islet Transplantation |
|---|---|
| NeutropeniaBlood and lymphatic system disorders | 4/36 |
| DiarrhoeaGastrointestinal disorders | 2/36 |
| PyrexiaGeneral disorders | 2/36 |
| PyelonephritisInfections and infestations | 2/36 |
| DehydrationMetabolism and nutrition disorders | 2/36 |
| AnaemiaBlood and lymphatic system disorders | 1/36 |
| Myocardial infarctionCardiac disorders | 1/36 |
| VertigoEar and labyrinth disorders | 1/36 |
| AscitesGastrointestinal disorders | 1/36 |
| GastritisGastrointestinal disorders | 1/36 |
| Event | Islet Transplantation |
|---|---|
| Mouth ulcerationGastrointestinal disorders | 33/36 |
| AnaemiaBlood and lymphatic system disorders | 29/36 |
| LeukopeniaBlood and lymphatic system disorders | 27/36 |
| DiarrhoeaGastrointestinal disorders | 23/36 |
| HeadacheNervous system disorders | 20/36 |
| NeutropeniaBlood and lymphatic system disorders | 19/36 |
| NauseaGastrointestinal disorders | 19/36 |
| VomitingGastrointestinal disorders | 15/36 |
| AcneSkin and subcutaneous tissue disorders | 15/36 |
| FatigueGeneral disorders | 14/36 |
| Age, Continuous(years) | Islet Transplantation |
|---|---|
| Mean | 40.9 ± 9.2 |
| Sex: Female, Male(Participants) | Islet Transplantation |
|---|---|
| Female | 14 |
| Male | 22 |
| Race/Ethnicity, Customized(Participants) | Islet Transplantation |
|---|---|
| Race: White | 35 |
| Race: Unspecified | 1 |
| Ethnicity: Non-Hispanic | 36 |
| Region of Enrollment(participants) | Islet Transplantation |
|---|---|
| United States | 19 |
| Canada | 4 |
| Germany | 4 |
| Italy | 4 |
| Switzerland | 5 |
| Number of Years with Diabetes(Years) | Islet Transplantation |
|---|---|
| Mean | 27 ± 10.4 |
| Daily Insulin Usage(Units of Insulin/kilogram/day (U/kg/day)) | Islet Transplantation |
|---|---|
| Mean | 0.5 ± 0.1 |
Plan to share: Yes — Data access is provided to the public in : 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools available to researchers; and 2.) TrialShare, the Immune Tolerance Network (ITN) portal.
This study is completed, as verified in Feb 2017. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
National Institute of Allergy and Infectious Diseases (NIAID)