AzTrials
AzTrials

Type 1 DiabetesPhase 1NCT01705899

Islet Allotransplantation in Type 1 Diabetes

A Phase 1 study testing Human Pancreatic Islets in people with Type 1 Diabetes, run by Ohio State University at 1 site in United States.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
Search all trials

Trial summary

Islet transplantation can provide physiologic insulin replacement to patients with type 1 diabetes without the complications associated with whole pancreas transplantation. The purpose of this study is to achieve insulin-independence in patients with type 1 diabetes, thereby eliminating the need for exogenous insulin… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Type 1 Diabetes
What is being tested?
Human Pancreatic Islets
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
Nov 2006to Oct 2033
Phase
Phase 1
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

  • Type 1 diabetes > 5 years
  • First islet transplant
  • Demonstrate intensive efforts to manage diabetes for last 6 months (≥4 SMBG/day, ≥3 injections of insulin/day or use of pump and ≥3 contacts with diabetes care team in last 12 months)
  • Metabolic complications: at least one of the following:
  • •Reduced hypoglycemia awareness (inability to sense hypoglycemia until blood glucose falls to < 54 mg/dl or > one hypoglycemic episode in last 12 months requiring outside help and not explained by clear precipitant)
  • •≥2 severe hypoglycemic events or ≥2 hospitalizations for diabetic ketoacidosis (DKA) in last year.
Show all 9Show fewer
  • Ability to provide written informed consent
  • Age 18-65
  • Specific for group 2: All of above (1-6) with renal transplant at least 6 months previous

Who cannot join

  • Age < 18 years or > 65 years
  • Inability to provide informed consent
  • Body Mass Index > 29 kg/m2
  • Insulin requirement of > 50 units/day
  • Stimulated C-peptide ≥ 0.2 ng/ml
  • Current panel reactive anti-HLA antibodies >20%
Show all 40Show fewer
  • Cardiovascular instability
  • Previous islet transplant
  • History of malignancy except squamous and basal cell skin cancer unless disease-free for > 2 years determined by independent oncologist
  • Active peptic ulcer disease
  • Condition that may interfere with absorption of medications
  • Hemoglobin A1C > 12%
  • Invasive aspergillus infection within one year
  • Varicella titer index <1.0
  • Rubella titer <10 IU/ml
  • Psychiatric disorder
  • Untreated hyperlipidemia: fasting total cholesterol >240 mg/dl, low density lipoprotein>130 mg/dl, or triglycerides >200 mg/dl
  • Hemoglobin <10 g/dl for females, and <11 g/dl for males, white blood cell count < 3,000/µL, platelet count of <150,000/microliter, CD4+ count <500/microliter
  • Liver function test abnormalities (if any value > 1.5 times normal, candidate will be excluded. If 1-1.5 times normal, test will be repeated. If re-test value remains above normal, candidate will be excluded).
  • Prostate specific antigen >4.0 ng/ml
  • Presence of gallstones, liver hemangioma, cirrhosis or evidence of portal hypertension
  • Untreated proliferative diabetic retinopathy
  • Females: positive pregnancy test, intent for future pregnancy, or any subject of reproductive age who is not surgically sterile and is unable or unwilling to use acceptable method of contraception
  • Female subjects who are breast-feeding
  • Adrenal insufficiency: 8am cortisol >19 mcg/dl adequate. Values 19 mcg/dl will be followed by Adreno-Corticotropic Hormone stimulation test
  • Any disease or condition that requires use of chronic steroids
  • Coagulopathy or use of chronic anticoagulation
  • Hyperthyroidism unless treated with radioactive iodine or surgery
  • Thyroid function tests outside normal range
  • Active alcoholism or other substance abuse within the past six months
  • History of non-adherence. Questionable adherence requires agreement entered and compliance demonstrated for at least 3 months
  • Active infection including hepatitis B or C, human immunodeficiency virus positive, positive Mantoux test [unless previously immunized with Bacillus Calmette-Guerin], or X-ray evidence of pulmonary infection
  • Inability to reach hospital within 6 hours of notification
  • Failure to clear psychological or psychiatric screen
  • Medical condition or circumstance that investigator finds will interfere with safe completion of the study
  • Receipt of previous transplant (excluding pancreas)
  • Creatinine clearance <50 ml/minute for females and <60 ml/minute for males or macroalbuminuria (>500 mg/24h)
  • Creatinine clearance <40ml/minute
  • Renal transplant in last 6 months
  • Current use of corticosteroids

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The Ohio State University Medical Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Islet transplantation can provide physiologic insulin replacement to patients with type 1 diabetes without the complications associated with whole pancreas transplantation. The purpose of this study is to achieve insulin-independence in patients with type 1 diabetes, thereby eliminating the need for exogenous insulin injections to maintain normal glucose levels, ameliorating severe hypoglycemia and potentially decreasing the development of diabetes-related complications. This study will investigate islet transplantation in subjects who have preserved renal function and subjects who have undergone cadaveric renal transplantation, since the latter subjects are already on immunosuppression.

This is a single center, prospective trial of islet transplantation in subjects receiving islets alone or islets after kidney transplant. This is a phase I study investigating the use of islet transplantation for the treatment of type 1 diabetes. Subjects will be eligible for an islet transplant if they meet all of the inclusion criteria and none of the exclusion criteria outlined in the protocol. In brief, the aims of this study are to establish an islet transplant program at the Ohio State University, determine the safety of islet transplantation in islet alone and kidney transplant recipients, determine whether islet transplantation will reduce the frequency of severe hypoglycemic events, determine whether a novel steroid-free immunosuppressive protocol will prevent rejection in islet transplants and to achieve insulin independence at one year after the final islet transplant.

Read the detailed description

Hypothesis - Insulin independence (insulin injections no longer needed) will be achieved in subjects with type 1 diabetes receiving islet transplantation using the immunosuppressive regimen of cyclosporine and sirolimus. Amelioration of severe hypoglycemia will also be achieved in these groups.

Primary Objective

To determine the safety of islet transplantation in islet alone and in kidney transplant recipients. Safety analyses include:

  • Incidence, timing and severity of adverse events and their relationship to the transplant protocol, islet infusion and immunosuppressive medications
  • Proportion without protocol-related serious adverse events (SAE) at 1 year
  • Incidence, type and severity of infectious complications
  • Incidence and severity of procedural-related events, such as bleeding and portal vein thrombosis
  • Incidence and severity of liver function test elevations
  • Incidence and severity of hypoglycemia
  • Incidence and severity of creatinine clearance and urine microalbumin changes
  • Incidence and severity of lipid abnormalities
  • Proportion of those who develop donor-specific alloantibody

Secondary Objective

To determine the efficacy of islet transplantation in islet alone and in kidney transplant recipients. Efficacy analyses include:

  • Time to insulin independence, defined as freedom from insulin use (insulin injections not needed) for 14 or more consecutive days
  • Proportion of those that achieve insulin independence at any time during the first year
  • Proportion of those one year after final transplant who have:
  • Positive C-peptide (≥0.3 ng/ml after stimulation)
  • Full function of their graft
  • Partial function of their graft
  • Marginal function of their graft
  • Mixed meal stimulated C-peptide >1.0 ng/ml at 6, and 12 months
  • Proportion of those that have an acute insulin response to glucose (AIRg) >20uU/ml during frequently sampled intravenous glucose tolerance test (FSIGT) at 6 and 12 months
  • Proportion of those with blood glucose level <140 mg/dl two hours after oral glucose tolerance test (OGTT) at 6 and 12 months
  • Proportion of those that have improved QOL at 6 and 12 months compared with baseline
  • Proportion of those that have improved hypoglycemia and glycemic lability scores at 6 and 12 months compared with baseline

Definition of full islet function:

  • Insulin independence
  • A1C ≤ 6.5%
  • Absence of severe hypoglycemic episodes
  • Fasting glucose ≥140 mg/dl less than 3 times a week
  • Post-prandial glucose (2 hours) >180 mg/dl less than 4 times a week

Definition of partial islet function:

  • Insulin requirement less than 50% of pre-transplant insulin requirement
  • C-peptide positive (≥0.3 ng/ml after stimulation)
  • A1C ≤ 6.5%
  • No severe hypoglycemia

Definition of marginal islet function:

  • C-peptide positive (≥0.3 ng/ml after stimulation)
  • A1C ≤ 7.5%
  • No severe hypoglycemia

This trial will have two study groups consisting of N=10 subjects with type 1 diabetes. One group (IA) will include subjects with preserved kidney function. A second group (IAK) will include subjects with renal failure secondary to diabetes who have received a prior kidney transplant at least 6 months previously and have stable renal function on a steroid-free immunosuppressive regimen.

Potential study participants will be recruited from the Endocrinology and Transplant clinics at the Ohio State University, and community physician referrals. Those who are potentially eligible will undergo a screening evaluation after review of the medical records. If the subject remains eligible, he/she will be enrolled in the islet transplant study and will be placed on a waiting list for an islet transplant. Once a transplant becomes available, the subject will be admitted to the hospital to undergo the transplant procedure. Frequent follow-up visits in the transplant clinic will occur throughout the following year after the transplant. Subjects will be closely monitored for adverse events and insulin requirements. If the subject does not achieve insulin independence, he/she may be eligible for a subsequent transplant.

There will be a 10-year enrollment with 12-month follow-up after last transplant. Since subjects may be eligible for a subsequent transplant within 18 months of the first transplant, the total duration may be up to 30 months after the first transplant in some subjects.

The study will be completed one year after the last islet transplant. Subjects who have undergone the islet transplant procedure and have completed the post-transplant evaluations one year after their last transplant will be considered to have completed the study.

Conditions
Type 1 Diabetes
Being tested
Human Pancreatic Islets
Keywords
Type 1 Diabetes, Islet transplant, Kidney transplant
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Human Pancreatic IsletsDrug

    Pancreatic islet tissue suspended in 150 - 300 ml of phenol red-free CMRL-1066 Transplant Media supplemented with 4% (w/v) HSA and 16mM HEPES in a 600ml transfer pack. Heparin will be administered at 70 IU/kg recipient body weight. Administered by intra-portal vein infusion. To be administered once, however, if full graft function is not achieved, a second or third dose of Pancreatic Islets may be given within 18 months of the first transplant.

Study groups in NCT01705899
Study groupRoleWhat they receive
Subjects with preserved kidney functionExperimentalSubjects with preserved renal function that have not previously received a kidney transplant will be treated with Human Pancreatic Islets (in the form of islets alone - IA).
Receives: Drug: Human Pancreatic Islets
Subjects with prior kidney transplantExperimentalSubjects with renal failure secondary to diabetes who have received a prior kidney transplant at least 6 months previously and have stable renal function on a steroid-free immunosuppressive regimen will receive Human Pancreatic Islets (in the form of islets after kidney - IAK).
Receives: Drug: Human Pancreatic Islets

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events

    Measured: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant

  2. Incidence of serious adverse events

    Serious adverse events will be defined (in accordance with FDA Title 21 CFR 312.32) as the following:

    • Death
    • Life-threatening and placing the subject at immediate risk of death
    • Hospitalization
    • Persistent or significant disability or incapacity
    • Congenital abnormal/birth defects
    • Requiring medical or surgical intervention to prevent permanent damage

    Measured: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant

  3. Incidence of infectious complications

    Measured: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant

  4. Incidence of procedural-related events

    Ex. Bleeding or portal vein thrombosis

    Measured: Day 1 post-transplant

  5. Incidence of elevated liver function tests

    Measured: Day 1 post-transplant

  6. Incidence of hypoglycemia

    Measured: Day 1 post-transplant

  7. Incidence of procedural-related events

    Ex. Bleeding or portal vein thrombosis

    Measured: Day 2 post-transplant

  8. Incidence of elevated liver function tests

    Measured: Day 2 post-transplant

  9. Incidence of hypoglycemia

    Measured: Day 2 post-transplant

  10. Incidence of procedural-related events

    Ex. Bleeding or portal vein thrombosis

    Measured: Day 3 post-transplant

  11. Incidence of elevated liver function tests

    Measured: Day 3 post-transplant

  12. Incidence of hypoglycemia

    Measured: Day 3 post-transplant

  13. Incidence of elevated liver function tests

    Measured: Day 5 post-transplant

  14. Incidence of hypoglycemia

    Measured: Day 5 post-transplant

  15. Incidence of elevated liver function tests

    Measured: Day 7 post-transplant

  16. Incidence of hypoglycemia

    Measured: Day 7 post-transplant

  17. Incidence of elevated liver function tests

    Measured: Day 10 post-transplant

  18. Incidence of hypoglycemia

    Measured: Day 10 post-transplant

  19. Incidence of elevated liver function tests

    Measured: Day 14 post-transplant

  20. Incidence of hypoglycemia

    Measured: Day 14 post-transplant

  21. Incidence of elevated liver function tests

    Measured: Day 21 post-transplant

  22. Incidence of hypoglycemia

    Measured: Day 21 post-transplant

  23. Incidence of abnormalities in lipids

    Measured: Day 28 post-transplant

  24. Incidence of elevated liver function tests

    Measured: Day 28 post-transplant

  25. Incidence of donor-specific antibody development

    Measured: Day 28 post-transplant

  26. Incidence of hypoglycemia

    Measured: Day 28 post-transplant

  27. Incidence of elevated liver function tests

    Measured: Day 42 post-transplant

  28. Incidence of hypoglycemia

    Measured: Day 42 post-transplant

  29. Incidence of elevated liver function tests

    Measured: Day 56 post-transplant

  30. Incidence of hypoglycemia

    Measured: Day 56 post-transplant

  31. Incidence of elevated liver function tests

    Measured: Day 90 post-transplant

  32. Incidence of hypoglycemia

    Measured: Day 90 post-transplant

  33. Incidence of abnormalities in lipids

    Measured: Day 90 post-transplant

  34. Incidence of donor-specific antibody development

    Measured: Day 90 post-transplant

  35. Incidence of elevated liver function tests

    Measured: Day 120 post-transplant

  36. Incidence of hypoglycemia

    Measured: Day 120 post-transplant

  37. Incidence of elevated liver function tests

    Measured: Day 180 post-transplant

  38. Incidence of hypoglycemia

    Measured: Day 180 post-transplant

  39. Incidence of abnormalities in lipids

    Measured: Day 180 post-transplant

  40. Incidence of donor-specific antibody development

    Measured: Day 180 post-transplant

  41. Incidence of elevated liver function tests

    Measured: Day 270 post-transplant

  42. Incidence of hypoglycemia

    Measured: Day 270 post-transplant

  43. Incidence of abnormalities in lipids

    Measured: Day 270 post-transplant

  44. Incidence of donor-specific antibody development

    Measured: Day 270 post-transplant

  45. Incidence of elevated liver function tests

    Measured: Day 365 post-transplant

  46. Incidence of abnormalities in lipids

    Measured: Day 365 post-transplant

  47. Incidence of hypoglycemia

    Measured: Day 365 post-transplant

  48. Incidence of donor-specific antibody development

    Measured: Day 365 post-transplant

  49. Change in microalbumin level

    Measured: Days 180 and 365 post-transplant

  50. Change in measured creatinine clearance

    Measured: Days 180 and 365 post-transplant

Secondary outcomes (8)

  1. Amount of daily insulin units required

    Measured: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant

  2. Measurement of C-peptide

    Measured: Days 1, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant

  3. Change in c-peptide level from fasting following administration of mixed meal

    Patients fasting c-peptide will be measured, then patient will be given a mixed meal of Ensure. The c-peptide level will be checked again at 90 minutes after administration of mixed meal.

    Measured: Days 180 and 365 post-transplant

  4. Change in acute insulin response to glucose

    As determined by oral glucose tolerance test and/or intravenous glucose tolerance test

    Measured: Days 180 and 365 post-transplant

  5. Incidence of blood glucose level <140mg/dl two hours after oral glucose tolerance tests

    Measured: Days 180 and 365 post-transplant

  6. Change in Quality of Life

    Measured: Days 180 and 365 post-transplant

  7. Change in hypoglycemia score

    Measured: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant

  8. Change in glycemic lability score

    Measured: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Oct 2012 (estimated)
  2. Study startNov 2006
  3. Primary completionOct 2033 (estimated)
  4. Study completionOct 2033 (estimated)

Why it stopped: Pausing of allotransplant program due to logistic issues.

Resources

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
Parallel groups
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01705899
Sponsor's protocol ID
IRB 2006H0200
Status last verified
Jan 2025
First submitted
3 May 2012
Last updated
16 Jan 2025
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No: Individual participant data for patients who agree is entered into a multi-center islet transplant data registry (no personally identifiable information will be shared). Upon completion of the study, results may also be published in a peer-reviewed journal.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Human Pancreatic Islets in people with Type 1 Diabetes, run by Ohio State University 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 40 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: paused, as of the sponsor's last update on 16 Jan 2025. 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?

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?

Incidence of adverse events (time frame: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant). The study lists 50 primary outcomes in all. 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 NCT01705899.

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 16 Jan 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in