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Type 1 Diabetes MellitusPhase 2NCT00315627

Steroid-free and Long-term Calcineurin-free Trial in Islet Cell Transplantation

A Phase 2 study testing Islet transplantation in people with Type 1 Diabetes Mellitus, 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

The purposes of this study are: 1. To reverse hyperglycemia and insulin dependency in patients with type 1 diabetes mellitus through islet transplantation utilizing steroid free, calcineurin-inhibitor free immunosuppression. 2. 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?
Islet transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
Jul 2005to Jan 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Potential candidates must have type 1 diabetes mellitus and fulfill one or more of the following:
  • Manifest signs and symptoms that are severe enough to be incapacitating. Incapacitating signs and symptoms include hypoglycemic episodes requiring assistance by others and hypoglycemia unawareness (the inability to recognize low blood glucoses; glucoses < 54 mg/dl). These patients are at high risk for involvement in accidents (they can lose consciousness or act irrationally), thus causing harm to themselves and/or others.
  • Patients with poor diabetes control (HbA1c > 8.0% but < 12%), despite intensive insulin therapy, as defined by: self monitoring of blood glucose ≥ 4 times/day, multiple insulin injections (≥ 3/day) or insulin pump, and close monitoring of blood glucose control by an endocrinologist. These patients can experience acute, rapid hyperglycemia secondary to several stress factors, that can lead to dehydration, disorientation, and in some instances, ketoacidosis.
  • Progressive diabetic complications. These patients with chronically poor glycemic control are at higher risk for the development of a wide variety of complications (retinopathy, neuropathy, nephropathy, and cardiovascular disease) associated with diabetes.

Who cannot join

  • Potential candidates will be excluded as per the following criteria:
  • Age < 18 or > 65 years
  • Duration of diabetes < 5 years
  • Do not have a physician that is monitoring diabetes for > 6 months
  • Body mass index > 26
  • Weight > 80 kg
Show all 41Show fewer
  • Insulin requirement > 1.0 u/kg/d
  • HbA1c > 12%
  • Stimulated or basal C-peptide > 0.3 ng/ml
  • Corrected creatinine clearance < 60 ml/min
  • Serum creatinine consistently above 1.6 mg/dl
  • Macroalbuminuria (> 300 mg/24 hours)
  • Anemia (hemoglobin < 12.0 g/dl for males; < 11 g/dl for females)
  • Hyperlipidemia (fasting low-density lipoprotein [LDL] cholesterol > 130 mg/dl and/or fasting triglycerides > 200 mg/dl)
  • Abnormal liver function tests (consistently > 1.5 x normal range)
  • Serological evidence of HIV, HBsAg and/or HBcAb, HBsAb without history of vaccination, human t cell lymphotropic virus 1 (HTLV-1), or hepatitis C virus (HCV)
  • Negative serology for Epstein-Barr virus (EBV) or evidence of acute or chronic infection (IgM ≥ IgG)
  • Lack of updated immunizations per current Centers for Disease Control (CDC) guidelines (including lack of immunization against hepatitis B, pneumococcus and influenza - during season)
  • Presence of panel reactive antibodies > 20%
  • Prostate-specific antigen (PSA) > 4 ng/ml unless malignancy is ruled out
  • Positive tuberculin test (unless proof of adequate treatment for latent tuberculosis can be provided)
  • X-ray evidence of pulmonary infection or other significant pathology
  • Gall stones and/or portal hypertension and/or hemangioma on liver ultrasound
  • Abnormal abdominal or pelvic ultrasound (evidence of masses that are considered suspicious for malignancy or adenopathy)
  • Active peptic ulcer disease
  • Active infections
  • Unstable cardiovascular status (including positive stress echocardiography if age > 35)
  • Untreated or unstable proliferative diabetic retinopathy
  • Previous/concurrent organ transplantation (except for failed islet cell or pancreas transplantation)
  • Malignancy or previous malignancy
  • Any medical condition requiring chronic use of steroids
  • Active alcohol or substance abuse; smoking in the last 6 months.
  • Sexually active females who are not:
  • post-menopausal,
  • surgically sterile, or
  • not using an acceptable method of contraception (oral contraceptives, Norplant, Depo-Provera, and barrier devices with spermicide are acceptable; condoms used alone are not acceptable)
  • Positive pregnancy test or intent for future pregnancy, or male subject's intent to procreate
  • Any condition or any circumstances that make it unsafe to undergo an islet cell transplant
  • Psychogenically unable to comply
  • Failed psychological evaluation
  • Persistent leukopenia (white blood cell count < 3,000/uL on more than 3 occasions)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Diabetes Research Institute

    Miami, Florida, 33136

Other trials in United States

About this study

The purposes of this study are:

  1. To reverse hyperglycemia and insulin dependency in patients with type 1 diabetes mellitus through islet transplantation utilizing steroid free, calcineurin-inhibitor free immunosuppression.
  2. To assess the long-term function of successful islet transplants in patients with type 1 diabetes mellitus utilizing islets that have undergone a period of culture.
  3. To determine whether the natural history of the microvascular, macrovascular, and neuropathic complications are altered following the successful transplantation of islets.
Read the detailed description

STUDY DESIGN:

The initial proposal submitted to the JDRFI was to compare 3 different groups of patients receiving islet cell transplants utilizing steroid-free, calcineurin-free protocols. The 3 groups were as follows:

  1. Zenapax, Rapamycin \& MMF
  2. Campath, Rapamycin \& MMF, and
  3. Thymoglobulin, Rapamycin \& MMF.

The grant was awarded in December 2003, however the recommendations were to focus on a single group (group 3 or 4) in order to determine the relative efficacy and toxicity of a new immunosuppressive drug combination. We elected to perform the group utilizing Campath, since we have a similar protocol utilizing the same immunosuppressive regimen with the addition of CD34+ enriched donor bone marrow cells (2000/0024). The results of this trial utilizing a steroid-free/calcineurin-free protocol will be compared with the standard "Edmonton Protocol" (2000/0196), which we are currently conducting (14 patients have been transplanted). In addition, the results will be compared with those in 2000/0024.

Protocol 2000/0024 (utilizing the same immunosuppressive regimen; Campath, Rapamycin, Tacrolimus-switched to MMF at 3 months) is being followed by a DSMB established at the NIH.

We propose to evaluate 12 patients with steroid free, long term calcineurin inhibitor free immunosuppression regimens which can be directly compared to our historical group of patients who underwent the Miami version of the Edmonton protocol (Islet Cell Transplantation Alone in Patients with Type 1 Diabetes Mellitus: Steroid-Free Immunosuppression - Protocol # 2000/196) and with the concurrent tolerogenic protocol (Islet Cell Transplantation Alone and CD34+ Enriched Donor Bone Marrow Cell Infusion in Patients with Type 1 Diabetes Mellitus; Steroid Free Regimen - Protocol # 2000/0024) which uses the same immunosuppressive regimen combined with CD34+ stem cell enriched donor bone marrow infusions.

The regimen will consist of Campath 1-H induction, maintenance immunosuppression with sirolimus and tacrolimus for 3 months with subsequent introduction of mycophenolate mofetil (MMF) and removal of tacrolimus completely and TNF-alpha inhibition (etanercept) in the peri-transplant period.

Being tested
Islet transplantation
Keywords
Islet Transplantation
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.

  • Islet transplantationDrug

    Also called islet

    Islet transplantation

Study groups in NCT00315627
Study groupRoleWhat they receive
islet transplantationExperimentalIslet Alone Transplantation under Alentuzumab (Campath1H) induction.
Receives: Drug: Islet transplantation

What is being measured

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

  1. Measurement of Glycemic Control by HbA1c and Prevention of Severe Hypoglycemia

    Number of subjects at 1 year with HbA1c < 6.5% and absence of severe hypoglycemia

    Measured: 1 year

Secondary outcomes (4)

  1. Islet Allograft Function

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

    Measured: 1 year

  2. Improvement in Metabolic Control as Evidenced by Hemoglobin A1c < 6.5%

    Number of subjects with a hemoglobin A1c < 6.5% at 1year after islet transplantation

    Measured: 1 year

  3. Elimination of Severe Hypoglycemia

    The number of subjects with severe hypoglycemia after transplantation

    Measured: 1 year

  4. Restoration of Hypoglycemia Awareness 1 Year After Transplantation

    The number of subjects with restoration of hypoglycemia awareness 1 year after islet transplantation

    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 posted18 Apr 2006 (estimated)
  2. Study startJul 2005
  3. Primary completionJan 2014
  4. Study completionJan 2014

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
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00315627
Sponsor's protocol ID
2004-0205
Status last verified
Apr 2017
First submitted
14 Apr 2006
Last updated
25 May 2017
Data monitoring committee
No
Individual data sharing
No

Publications

  • Froud T, Baidal DA, Faradji R, Cure P, Mineo D, Selvaggi G, Kenyon NS, Ricordi C, Alejandro R. Islet transplantation with alemtuzumab induction and calcineurin-free maintenance immunosuppression results in improved short- and long-term outcomes. Transplantation. 2008 Dec 27;86(12):1695-701. doi: 10.1097/TP.0b013e31819025e5.

    PubMed 19104407

  • 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 Islet transplantation in people with Type 1 Diabetes Mellitus, 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 4 inclusion and 41 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 25 May 2017. 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?

Yes. Results are posted in the registry (first posted 25 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Measurement of Glycemic Control by HbA1c and Prevention of Severe Hypoglycemia (time frame: 1 year). 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 NCT00315627, which also lists 2 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 25 May 2017.

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