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Diabetes Mellitus, Type IPhase 2NCT00306098

Islet Cell Transplantation Alone in Patients With Type 1 Diabetes Mellitus: Steroid-Free Immunosuppression

A Phase 2 study testing islets in people with Diabetes Mellitus, Type I, run by Rodolfo Alejandro at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

SPECIFIC AIMS: 1. To reverse hyperglycemia and insulin dependency in patients with Type 1 Diabetes Mellitus by islet cell transplantation; 2. To eliminate the incidence of hypoglycemia coma and unawareness in patients with Type 1 Diabetes Mellitus by islet cell transplantation; 3. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Diabetes Mellitus, Type I
What is being tested?
islets
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
Dec 2000to 4 Jul 2004
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

  • Patients between 18 and 65 years of age
  • Patients with type 1 diabetes mellitus for more than 5 years duration
  • One or more of the following:
  • Hypoglycemia unawareness - judged by history of blood sugars <54 on glucometer without symptoms and/or hypoglycemic episodes requiring assistance from either family, glucagon administration or emergency services
  • Poor diabetes control (HbA1c>8% or >2 visits/yr to hospital for treatment of ketoacidosis) despite intensive insulin therapy
  • Progressive complications of type 1 diabetes mellitus
  • Body Mass Index (BMI) ≤26

Who cannot join

  • c-peptide > 0.3ng/ml basal or stimulated;
  • untreated proliferative diabetic retinopathy;
  • HbA1C >12%;
  • creatinine clearance <60;
  • serum creatinine consistently >1.6 mg/dl;
  • macroalbuminuria >300mg albumin in 24 hours;
Show all 22Show fewer
  • presence of panel reactive antibodies (PRA) >20%;
  • previous/concurrent organ transplantation (except previous unsuccessful islet cell transplant;
  • malignancy or previous malignancy (except non-melanomatous skin cancer);
  • x-ray evidence of pulmonary infection;
  • active infections;
  • active peptic ulcer disease, gall stones, hemangioma, or portal hypertension
  • serological evidence of HIV, HbsAg or HCV; serological evidence of active EBV (IgM>IgG) or EBV negative serology;
  • PPD conversion or positive PPD without historic completion of appropriate prophylactic treatment;
  • abnormal liver function test;
  • anemia (hemoglobin <12.0);
  • hyperlipidemia (fasting serum triglycerides >200mg/dl and/or fasting serum cholesterol >240 mg/dl and/or fasting LDL cholesterol >140 mg/dl);
  • BMI above 26;
  • unstable cardiovascular status; prostate specific antigen (PSA) >4;
  • pregnancy or breastfeeding;
  • sexually-active females who are not: a) post-menopausal, b) surgically sterile, or c) not using an acceptable method of contraception (oral contraceptives, Norplant, Depo-Provera, and barrier devices are acceptable; condoms used alone are not acceptable);
  • alcohol abuse, substance abuse or smoking within the previous 6 months; insulin requirement >1u/kg/day and any condition or any circumstance that makes it unsafe to undergo an islet cell transplant.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Miami, Diabetes Research Institute

    Miami, Florida, 33136

Other trials in United States

About this study

SPECIFIC AIMS:

  1. To reverse hyperglycemia and insulin dependency in patients with Type 1 Diabetes Mellitus by islet cell transplantation;
  2. To eliminate the incidence of hypoglycemia coma and unawareness in patients with Type 1 Diabetes Mellitus by islet cell transplantation;
  3. To assess long-term safety and function of successful islet cell transplants in patients with Type 1 Diabetes Mellitus;
  4. To determine whether the natural history of the microvascular, macrovascular and neuropathic complications of Diabetes Mellitus are altered following successful transplantation of islet cells; and
  5. To assess the effect of infliximab in preventing early islet destruction, and thereby eliminating the need for a second donor's islet cells.
  6. To assess the effect of etanercept in preventing early islet destruction.
  7. To assess the effect of exenatide to improve islet graft function and survival in subjects that have returned to using exogenous insulin.
  8. To assess the ability of exenatide to improve islet survival at time of transplantation.
Read the detailed description

This Phase II trial will have 3 groups: Group A will receive islets from 2 donors and will not receive infliximab. Group B will receive, in addition to Daclizumab, Sirolimus, and Tacrolimus, a dose of infliximab and islets from a single donor, as per the Edmonton protocol. Everything else about the clinical trial will be the same for both groups. The first 4 patients will be assigned to Group A, the next 4 patients to Group B, the next 4 patients to Group A, and the next 4 patients to Group B (total =16). Patients in Group A will receive 1-2 transplants with cells from 2 donors. If the second donor pancreas is received and satisfactory at the same time as the first pancreas, one islet infusion will be used to infuse cells from both donors. If the second pancreas is not received until after the first transplantation, a second islet infusion will be done. A second course of five doses of Daclizumab will be started on the day of the second islet infusion).

In order to determine if prolonged administration of etanercept, in combination with transplantation of cultured islets, will prevent TNF-α production and enhance engraftment, we have added Group C to the current protocol. Group C, in addition to Daclizumab, Sirolimus, and Tacrolimus, will receive Etanercept in the peri-transplant period and islets from one or more donors. The last 24 patients included in this Protocol will be in Group C if they are new, or in Group A and B Supplemental Infusion if they had previous transplants. Any Group A or B participants who are eligible for a supplemental infusion will receive etanercept but no infliximab.

Being tested
islets
Keywords
Transplantation, Islets of Langerhans
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.

  • isletsDrug

    Also called islet transplantation

    Intraportal infusion of islets

Study groups in NCT00306098
Study groupRoleWhat they receive
Islet transplantationExperimentalSubjects receiving intraportal Islet cell infusion (transplant)
Receives: Drug: islets

What is being measured

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

  1. a1c less than 6.5 without severe hypoglycemia

    number of subjects with a1c less than 6.5 without severe hypoglycemia

    Measured: for the duration of islet graft function

Secondary outcomes (5)

  1. partial graft function, as evidenced by baseline C-peptide greater than 0.5 ng/ml

    Number of subjects with basal c-peptide greater than 0.5 ng/ml

    Measured: 1 year

  2. reduction in insulin requirements in those patients who do not achieve insulin independence

    Number of subjects with at least 40% reduction in insulin requirements

    Measured: 1 year

  3. improvement in metabolic control as evidenced by improvement in: HbA1C (less or equal to 7)

    Number of subjects with HBA1C less or equal to 7

    Measured: 1 year

  4. elimination or reduction in the incidence of hypoglycemic coma or unawareness

    Number of subjects without severe hypoglycemia

    Measured: 1 year

  5. assessment of efficacy of infliximab in preventing early rejection -

    number of subjects achieving insulin independence with a single infusion of infliximab vs no infliximab

    Measured: 1 year

Timeline

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

  1. First posted22 Mar 2006 (estimated)
  2. Study startDec 2000
  3. Primary completion4 Jul 2004
  4. Study completion4 Jul 2004

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00306098
Sponsor's protocol ID
20000196
Other IDs
1U42RR016603-01, HRSA # 1 R38OT01367-01-00, No Number
Status last verified
Oct 2024
First submitted
17 Mar 2006
Last updated
4 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Froud T, Ricordi C, Baidal DA, Hafiz MM, Ponte G, Cure P, Pileggi A, Poggioli R, Ichii H, Khan A, Ferreira JV, Pugliese A, Esquenazi VV, Kenyon NS, Alejandro R. Islet transplantation in type 1 diabetes mellitus using cultured islets and steroid-free immunosuppression: Miami experience. Am J Transplant. 2005 Aug;5(8):2037-46. doi: 10.1111/j.1600-6143.2005.00957.x.

    PubMed 15996257

  • Faradji RN, Froud T, Messinger S, Monroy K, Pileggi A, Mineo D, Tharavanij T, Mendez AJ, Ricordi C, Alejandro R. Long-term metabolic and hormonal effects of exenatide on islet transplant recipients with allograft dysfunction. Cell Transplant. 2009;18(10):1247-59. doi: 10.3727/096368909X474456.

    PubMed 20003758

  • Tharavanij T, Betancourt A, Messinger S, Cure P, Leitao CB, Baidal DA, Froud T, Ricordi C, Alejandro R. Improved long-term health-related quality of life after islet transplantation. Transplantation. 2008 Nov 15;86(9):1161-7. doi: 10.1097/TP.0b013e31818a7f45.

    PubMed 19005394

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing islets in people with Diabetes Mellitus, Type I, run by Rodolfo Alejandro 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 22 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 4 Nov 2024. 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 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?

a1c less than 6.5 without severe hypoglycemia (time frame: for the duration of islet graft function). 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 NCT00306098, which also lists 3 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 2024.

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