Diabetes MellitusPhase 1NCT00706420
Islet Transplantation Alone (ITA) in Patients With Difficult to Control Type I Diabetes Mellitus Using a Glucocorticoid-free Immunosuppressive Regimen
A Phase 1 study testing Islet Transplantation + Immunosuppression and Islet cell transplantation in people with Diabetes Mellitus, run by City of Hope Medical Center at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the safety and effectiveness of islet cell transplantation alone (ITA) in patients with difficult to control type I diabetes. Difficult to control type 1 diabetes is defined as wide swings in blood glucose that disrupt the patient's life and result in frequent episodes of low… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- Islet Transplantation + Immunosuppression and Islet cell transplantation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Apr 2004to 13 Sep 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Difficult to control Type 1 diabetes mellitus (defined above). Documentation of negative basal and stimulated C-peptide (a basal level of < 0.2 ng/ml before IV administration of 1 mg of glucagon, and a glucagon stimulated C-peptide < 0.8 ng/ml) and diagnosis of diabetes for at least 5 years. When possible, patients will be evaluated with continuous glucose monitoring (GlucoseSensor ®) to determine the frequency and extent of hypo- and hyperglycemic episodes.
- No evidence of chronic renal failure or significant proteinuria (serum creatinine < 1.6 mg/dl, creatinine clearance >80 ml/min, and albumin excretion </= 300 mg/24 hr).
- No evidence of liver disease (liver enzymes < twice the upper limit of normal for each of ALT and AST, bilirubin < 2 mg/dl, albumin > 3.5 g/dl, and PT and PTT </= 1.1 x the upper limit of normal).
- Frequent episodes of symptomatic hypoglycemia (i.e. loss of consciousness, headaches, anxiety, irritability, trembling, sweating) more than once per week, documented hypoglycemic unawareness (i.e. no adrenergic and/or neurogenic symptoms with blood glucose < 54 mg/dl) two or more times in the past two months, or hypoglycemic episodes that required the assistance of another person more than once per month or hospitalization more than once over the past 20 months.
- Ability to comply with post-transplant regimen, including immunosuppression, insulin pump therapy and metabolic testing. Patients will be required to perform self-monitoring of blood glucose a minimum of four times daily, and provide complete records of blood glucose levels and insulin doses.
- Ability to give informed consent.
- Age greater than or equal to 18 years or less than or equal to 65 years.
Who cannot join
- Significant liver disease (including elevation of liver enzymes > twice the upper limit of normal for each of ALT and AST, bilirubin > 2 mg/dl, albumin < 3.5 g/dl, liver masses, portal vein thrombosis, evidence of portal hypertension, or significant, untreated gallbladder disease (i.e. gallstones).
- Significant cardiovascular disease, including non-correctable coronary artery disease with ejection fraction < 50% and/or recent myocardial infarction (within last 12 months); extensive peripheral vascular disease not correctable by surgery or untreated proliferative retinopathy.
- Recent unresolved acute infection, or chronic infection, including tuberculosis, HIV, HBV, HCV, CMV or positive skin test for TB.
- Any history of malignancy, except squamous or basal skin cancer or in situ cancer of the cervix.
- Recent history of non-compliance, or inability to demonstrate capacity to comply with strict blood glycemic control and insulin pump therapy.
- Psychiatric illness that is untreated, or likely to interfere significantly with transplantation despite treatment.
Show all 15Show fewer
- Presence of preformed antibodies on panel reactive antibody screening > 20%.
- Body mass index (BMI) greater than 30.
- Age less than 18 years or greater than 65 years.
- Presence of a chronic disease that must be chronically treated with one or more of the following medications: glucocorticoids, diazoxide, bumetanide, haloperidol, chlorpromazine, desipramine, doxepin, imipramine, isoproterenol, levodopa, morphine, L-asparaginase, cyclophosphamide, isoniazid, heparin, nalidixic acid, or any other agents that may adversely influence glycemic control and which may confound the interpretation of Graft Success post-transplant.
- Pregnant women, women intending future pregnancy, women of reproductive potential who are unable or unwilling to follow effective contraceptive measures for the duration of immunosuppressive therapy, and women presently breast feeding are ineligible due to the unknown effects of these drugs on the fetus and nursing infant.
- Active alcohol or substance abuse, including cigarette smoking (must be abstinent for > 3 months).
- Hyperlipidemia (total cholesterol > 260 mg/dl, LDL > 130 mg/dl, and/or triglycerides > 300 mg/dl) despite appropriate treatment.
- Anemia (Hgb < 12 g/dl) or other hematologic disorders that require medical attention.
- Increased risk of bleeding (platelet count < 80,000; INR > 1.5), other chronic hemostasis disorders, or treatment with chronic anticoagulant therapy (i.e. heparin or warfarin).
Trial locations and contacts
1 site in 1 country.
United States1 site
City of Hope Medical Center
Duarte, California, 91010
About this study
The purpose of this study is to evaluate the safety and effectiveness of islet cell transplantation alone (ITA) in patients with difficult to control type I diabetes. Difficult to control type 1 diabetes is defined as wide swings in blood glucose that disrupt the patient's life and result in frequent episodes of low blood glucose despite the proper use of standard insulin therapy and frequent blood glucose monitoring.
Read the detailed description
Type 1 diabetes is associated with the damage of a specific cell subtype of pancreatic islets (clusters of cells in the pancreas that produce insulin and other metabolic hormones), which makes patients depend on an outside source of insulin. Despite insulin treatment, type 1 diabetes mellitus causes a significant risk of long-term problems, including damage to the heart, blood vessels, nerves, eyes and kidneys. The results of recent research studies suggest that these complications are caused by poor glucose control.
Transplantation of islets offers the prospect of good glycemic (blood glucose) control without the major surgical risks associated with whole pancreas transplant and may result in not needing any insulin injections. In 2000, a group of investigators in Edmonton, Canada showed that islet transplantation using a combination of anti-rejection drugs to help prevent the rejection of transplanted islets was effective in eliminating insulin intake in 7 subjects who were followed up to 20 months. After 5 years, more than 60 patients have been transplanted at Edmonton and only 1 in 10 remained off of insulin.
This study is being performed to confirm the results of the Edmonton study to see if islet transplantation alone (ITA) is a safe and effective way of treating subjects with type 1 diabetes. This study uses a few additional medications and vitamin supplements that were not included in the original Edmonton study. We hope this will improve the long-term outcome of islet transplantation.
- Conditions
- Diabetes Mellitus
- Being tested
- Islet Transplantation + Immunosuppression, Islet cell transplantation
- Keywords
- Diabetes Mellitus, Islet Transplantation Alone, Glucocorticoid-free Immunosuppressive Regimen
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Islet Transplantation + ImmunosuppressionProcedure or surgery
Islet Transplantation + Immunosuppression (Sirolimus/Tacrolimus, daclizumab)
Islet cell transplantationBiological
Islet cell transplantation will occur through the portal vein.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Islet cell transplantation alone Receives: Procedure: Islet Transplantation + Immunosuppression; Biological: Islet cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of subjects who have achieved insulin independence post transplant.
Measured: 3, 6, 12, and 24 months
Secondary outcomes (4)
Stimulated C-peptide response >0.6 ng/ml
Measured: 3, 6, 12, and 24 months
Insulin use </=0.2units/kg/day
Measured: 3, 6, 12, and 24 months
Reduction/elimination of hypoglycemic episodes
Measured: 3, 6, 12, and 24 months
HgAlc</= 6.5%
Measured: 3, 6, 12, and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2008 (estimated)
- Study start7 Apr 2004
- Primary completion13 Sep 2027 (estimated)
- Study completion13 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Fouad Kandeel, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00706420
- Sponsor's protocol ID
- 01083
- Other IDs
- RR-01-002
- Status last verified
- Nov 2026
- First submitted
- 25 Jun 2008
- Last updated
- 4 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000 Jul 27;343(4):230-8. doi: 10.1056/NEJM200007273430401.
PubMed 10911004Ryan EA, Paty BW, Senior PA, Bigam D, Alfadhli E, Kneteman NM, Lakey JR, Shapiro AM. Five-year follow-up after clinical islet transplantation. Diabetes. 2005 Jul;54(7):2060-9. doi: 10.2337/diabetes.54.7.2060.
PubMed 15983207Wang CH, Orr C, Hacker-Stratton J, El-Shahawy M, Omori K, Qi M, Kandeel F. Shorter Digestion Times of Donor Islets Is Associated With Better Islet Graft Function After Islet Transplantation. Cell Transplant. 2025 Jan-Dec;34:9636897241310989. doi: 10.1177/09636897241310989.
PubMed 39881535Orr C, Stratton J, El-Shahawy M, Forouhar E, Peng A, Singh G, Omori K, Qi M, Kandeel F. Impact of Tacrolimus, Sirolimus, Age, and Body Mass Index on the Occurrence of Skin Cancer and Islet Dysfunction After Transplantation. Cell Transplant. 2025 Jan-Dec;34:9636897241309412. doi: 10.1177/09636897241309412.
PubMed 39780302
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Islet Transplantation Alone (ITA) in Patients With Difficult to Control Type I Diabetes Mellitus Using a Glucocorticoid-free Immunosuppressive Regimen
- ClinicalTrials.gov ID
- NCT00706420
- Acronym / sponsor ID
- 01083
- Conditions
- Diabetes Mellitus
- Keywords
- Diabetes Mellitus, Islet Transplantation Alone, Glucocorticoid-free Immunosuppressive Regimen
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 17 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 7 Apr 2004 (actual)
- Primary completion
- 13 Sep 2027 (estimated)
- Study completion
- 13 Sep 2027 (estimated)
- First posted
- 27 Jun 2008 (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.
The purpose of this study is to evaluate the safety and effectiveness of islet cell transplantation alone (ITA) in patients with difficult to control type I diabetes. Difficult to control type 1 diabetes is defined as wide swings in blood glucose that disrupt the patient's life and result in frequent episodes of low blood glucose despite the proper use of standard insulin therapy and frequent blood glucose monitoring.
Detailed description
Type 1 diabetes is associated with the damage of a specific cell subtype of pancreatic islets (clusters of cells in the pancreas that produce insulin and other metabolic hormones), which makes patients depend on an outside source of insulin. Despite insulin treatment, type 1 diabetes mellitus causes a significant risk of long-term problems, including damage to the heart, blood vessels, nerves, eyes and kidneys. The results of recent research studies suggest that these complications are caused by poor glucose control.
Transplantation of islets offers the prospect of good glycemic (blood glucose) control without the major surgical risks associated with whole pancreas transplant and may result in not needing any insulin injections. In 2000, a group of investigators in Edmonton, Canada showed that islet transplantation using a combination of anti-rejection drugs to help prevent the rejection of transplanted islets was effective in eliminating insulin intake in 7 subjects who were followed up to 20 months. After 5 years, more than 60 patients have been transplanted at Edmonton and only 1 in 10 remained off of insulin.
This study is being performed to confirm the results of the Edmonton study to see if islet transplantation alone (ITA) is a safe and effective way of treating subjects with type 1 diabetes. This study uses a few additional medications and vitamin supplements that were not included in the original Edmonton study. We hope this will improve the long-term outcome of islet transplantation.
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 | Procedure: Islet Transplantation + Immunosuppression, Biological: Islet cell transplantationIslet cell transplantation alone |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Difficult to control Type 1 diabetes mellitus (defined above). Documentation of negative basal and stimulated C-peptide (a basal level of < 0.2 ng/ml before IV administration of 1 mg of glucagon, and a glucagon stimulated C-peptide < 0.8 ng/ml) and diagnosis of diabetes for at least 5 years. When possible, patients will be evaluated with continuous glucose monitoring (GlucoseSensor ®) to determine the frequency and extent of hypo- and hyperglycemic episodes.
- No evidence of chronic renal failure or significant proteinuria (serum creatinine < 1.6 mg/dl, creatinine clearance >80 ml/min, and albumin excretion </= 300 mg/24 hr).
- No evidence of liver disease (liver enzymes < twice the upper limit of normal for each of ALT and AST, bilirubin < 2 mg/dl, albumin > 3.5 g/dl, and PT and PTT </= 1.1 x the upper limit of normal).
- Frequent episodes of symptomatic hypoglycemia (i.e. loss of consciousness, headaches, anxiety, irritability, trembling, sweating) more than once per week, documented hypoglycemic unawareness (i.e. no adrenergic and/or neurogenic symptoms with blood glucose < 54 mg/dl) two or more times in the past two months, or hypoglycemic episodes that required the assistance of another person more than once per month or hospitalization more than once over the past 20 months.
- Ability to comply with post-transplant regimen, including immunosuppression, insulin pump therapy and metabolic testing. Patients will be required to perform self-monitoring of blood glucose a minimum of four times daily, and provide complete records of blood glucose levels and insulin doses.
Key exclusion criteria (15 listed)
- Significant liver disease (including elevation of liver enzymes > twice the upper limit of normal for each of ALT and AST, bilirubin > 2 mg/dl, albumin < 3.5 g/dl, liver masses, portal vein thrombosis, evidence of portal hypertension, or significant, untreated gallbladder disease (i.e. gallstones).
- Significant cardiovascular disease, including non-correctable coronary artery disease with ejection fraction < 50% and/or recent myocardial infarction (within last 12 months); extensive peripheral vascular disease not correctable by surgery or untreated proliferative retinopathy.
- Recent unresolved acute infection, or chronic infection, including tuberculosis, HIV, HBV, HCV, CMV or positive skin test for TB.
- Any history of malignancy, except squamous or basal skin cancer or in situ cancer of the cervix.
- Recent history of non-compliance, or inability to demonstrate capacity to comply with strict blood glycemic control and insulin pump therapy.
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 |
|---|---|---|
| Islet Transplantation + ImmunosuppressionIslet Transplantation + Immunosuppression (Sirolimus/Tacrolimus, daclizumab) | Procedure or surgery | 1 |
| Islet cell transplantationIslet cell transplantation will occur through the portal vein. | Biological | 1 |
Primary outcome
Percent of subjects who have achieved insulin independence post transplant.
Time frame: 3, 6, 12, and 24 months
4 secondary outcomes
Stimulated C-peptide response >0.6 ng/ml
Time frame: 3, 6, 12, and 24 months
Insulin use </=0.2units/kg/day
Time frame: 3, 6, 12, and 24 months
Reduction/elimination of hypoglycemic episodes
Time frame: 3, 6, 12, and 24 months
HgAlc</= 6.5%
Time frame: 3, 6, 12, and 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
- Background: PubMed 10911004Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000 Jul 27;343(4):230-8. doi: 10.1056/NEJM200007273430401.
- Background: PubMed 15983207Ryan EA, Paty BW, Senior PA, Bigam D, Alfadhli E, Kneteman NM, Lakey JR, Shapiro AM. Five-year follow-up after clinical islet transplantation. Diabetes. 2005 Jul;54(7):2060-9. doi: 10.2337/diabetes.54.7.2060.
- Derived from this study: PubMed 39881535Wang CH, Orr C, Hacker-Stratton J, El-Shahawy M, Omori K, Qi M, Kandeel F. Shorter Digestion Times of Donor Islets Is Associated With Better Islet Graft Function After Islet Transplantation. Cell Transplant. 2025 Jan-Dec;34:9636897241310989. doi: 10.1177/09636897241310989.
- Derived from this study: PubMed 39780302Orr C, Stratton J, El-Shahawy M, Forouhar E, Peng A, Singh G, Omori K, Qi M, Kandeel F. Impact of Tacrolimus, Sirolimus, Age, and Body Mass Index on the Occurrence of Skin Cancer and Islet Dysfunction After Transplantation. Cell Transplant. 2025 Jan-Dec;34:9636897241309412. doi: 10.1177/09636897241309412.
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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.
Fouad Kandeel, MD principal investigator
City of Hope Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Islet Transplantation + Immunosuppression and Islet cell transplantation in people with Diabetes Mellitus, run by City of Hope Medical Center 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 7 inclusion and 15 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: under way, not looking for participants, as of the sponsor's last update on 4 Nov 2026. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Percent of subjects who have achieved insulin independence post transplant. (time frame: 3, 6, 12, and 24 months). 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 NCT00706420, which also lists 4 linked publications.
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 4 Nov 2026.