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Type 1 DiabetesPhase 1/2NCT00285194

hOKT3γ1 (Ala-Ala) Combined With Sirolimus and Delayed Tacrolimus in Type 1 Diabetic Islet Allograft Recipients

A Phase 1/2 study testing Allogeneic Islets of Langerhans and hOKT3γ1 (Ala-Ala) in people with Type 1 Diabetes and Hypoglycemia, run by University of Minnesota 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 collective effects of two-layer pancreas preservation, pretransplant islet culture, day -2 pretransplant immunosuppression, and induction immunosuppression with the FcR-nonbinding anti-CD3 monoclonal antibody hOKT3γ1 (Ala-Ala)to facilitate diabetes reversal after single-donor islet transplantation. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Type 1 Diabetes, Hypoglycemia
What is being tested?
Allogeneic Islets of Langerhans and hOKT3γ1 (Ala-Ala)
How many people
6 participants
Where
1 siteUnited States
Study dates
Apr 2000to Jan 2004
Phase
Phase 1/2
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
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Primary islet allotransplant
  • Type 1 diabetes mellitus, complicated by at least one of the following situations that persist despite intensive efforts in close cooperation with their diabetes care team:
  • Metabolic lability/instability;
  • Reduced awareness of hypoglycemia;
  • Persistently poor glucose control (as defined by HgbA1c>10% at the end of six months of intensive management efforts with the diabetes care team);
  • Progressive secondary complications.
  • Age 18 and older
  • Able to give written informed consent

Who cannot join

  • Age less than 18 years
  • Body weight greater than75 kg.
  • BMI greater than 26 kg/m2 for male and females
  • Waist-to-hip ratio 0.80 (female) and 0.95 (male)
  • First degree relative with type 2 diabetes
  • Insulin requirement of greater than 0.7 IU/kg/day
Show all 38Show fewer
  • HbA1C greater than 12%
  • Positive C-peptide response to intravenous arginine stimulation
  • Untreated proliferative retinopathy
  • Macroalbuminuria (urinary albumin excretion greater than 300 mg/24hrs)
  • Creatinine clearance greater than 85 ml/min/1.73 m2 in females, greater than 95 ml/min/1.73 m2 in males
  • Serum creatinine greater than 1.2 mg/dl
  • Previous pancreas or islet transplant
  • Previous OKT3 antibody therapy
  • Presence of history of panel-reactive anti-HLA antibodies greater than 10%
  • Abnormal T4 and TSH despite thyroid replacement therapy
  • Positive pregnancy test, or presently breast-feeding
  • Active infection
  • Negative screen for Epstein-Barr Virus (EBV) by an EBNA method
  • Invasive aspergillus infection within year prior to study entry
  • Any history of malignancy
  • Active alcohol or substance abuse
  • History of non-adherence to prescribed regimens
  • Psychiatric disorder making the subject not a suitable candidate for transplantation
  • Karnofsky performance score greater than 70
  • Baseline Hgb greater than 11.7 g/dl; lymphopenia (greater than 1,000/L), or leukopenia (greater than 4,000 total leukocytes/L), or an absolute CD4+ count <500/L
  • Thrombocytopenia greater than 150 x 109/L
  • Use of warfarin or other anticoagulant therapy (except aspirin) or patient with PT-INR greater than 1.5
  • Severe co-existing cardiac disease
  • Baseline liver function tests outside of normal range
  • Presence of gallstones on baseline ultrasound exam
  • Active peptic ulcer disease
  • Severe unremitting diarrhea or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications
  • Celiac disease
  • Hyperlipidemia (fasting LDL cholesterol greater than 130 mg/dl, treated or untreated; and/or fasting triglycerides greater than 200 mg/dl)
  • Addison's disease.
  • Under treatment for a medical condition requiring chronic use of systemic steroids
  • Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Universtiy of Minnesota

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

The collective effects of two-layer pancreas preservation, pretransplant islet culture, day -2 pretransplant immunosuppression, and induction immunosuppression with the FcR-nonbinding anti-CD3 monoclonal antibody hOKT3γ1 (Ala-Ala)to facilitate diabetes reversal after single-donor islet transplantation.

Read the detailed description

This is an open-label, one-year follow-up study of type 1 diabetic islet allograft recipients who receive FcR non-binding OKT3 antibody hOKT3γ1 (Ala-Ala) plus sirolimus induction immunotherapy combined with sirolimus and delayed tacrolimus maintenance immunosuppression. Six subjects were transplanted.

The premise behind the proposal is that hOKT3γ1(Ala-Ala) corrects the imbalance between autoreactive and regulatory T cells and consequently prevents autoimmune destruction of transplanted islets. To prevent allorejection, hOKT3γ1(Ala-Ala)was combined with sirolimus and delayed tacrolimus. Additionally, the safety and efficacy of the maintenance immunosuppressive regimen of sirolimus combined with tacrolimus was monitored.

Being tested
Allogeneic Islets of Langerhans, hOKT3γ1 (Ala-Ala)
Medical subject headings
Diabetes Mellitus, Type 1, Hypoglycemia

What participants receive

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

  • Allogeneic Islets of LangerhansDrug

  • hOKT3γ1 (Ala-Ala)Drug

What is being measured

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

  1. Safety, tolerability, immune activity, and pharmacokinetics of hOKT3γ1 (Ala-Ala) antibody induction therapy for the prevention of autoimmune destruction and rejection of allogeneic islet transplants as measured by:

  2. -Physical examination

  3. -Vital signs

  4. -Body weight

  5. -Adverse events

  6. -Laboratory and diagnostic safety assessments included complete blood counts with differential and platelets, circulating T cell phenotypes, and serum chemistry.

  7. -Immune activity and pharmacokinetic assessments included hOKT3γ1 (Ala-Ala) level and half-life, monoclonal antibody coating and modulation of CD3 on peripheral blood T cells, and anti-hOKT3γ1 (Ala-Ala) antibody responses.

Secondary outcomes (4)

  1. Efficacy of hOKT3γ1 (Ala-Ala) antibody induction therapy for the prevention of autoimmune destruction and rejection of islet transplants as defined by:

  2. -Proportion of subjects with full islet graft function (insulin independence and HbA1c <7%);

  3. -Proportion of subjects with partial islet graft function (insulin dependence, basal or arginine-stimulated C-peptide levels of greater or equal to 0.5 ng/ml and HbA1c <7%);

  4. -Proportion of subjects with slet graft loss will be defined as a return to insulin therapy for >30 days, absence of basal and arginine-stimulated C-peptide, re-transplantation, or patient death;

Timeline

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

  1. First posted1 Feb 2006 (estimated)
  2. Study startApr 2000
  3. Primary completionJan 2004
  4. Study completionJan 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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00285194
Sponsor's protocol ID
0003M44181
Status last verified
Jul 2012
First submitted
30 Jan 2006
Last updated
2 Aug 2012
Results posted
No
Data monitoring committee
Yes

Publications

  • Hering BJ, Kandaswamy R, Harmon JV, Ansite JD, Clemmings SM, Sakai T, Paraskevas S, Eckman PM, Sageshima J, Nakano M, Sawada T, Matsumoto I, Zhang HJ, Sutherland DE, Bluestone JA. Transplantation of cultured islets from two-layer preserved pancreases in type 1 diabetes with anti-CD3 antibody. Am J Transplant. 2004 Mar;4(3):390-401. doi: 10.1046/j.1600-6143.2003.00351.x.

    PubMed 14961992

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Allogeneic Islets of Langerhans and hOKT3γ1 (Ala-Ala) in people with Type 1 Diabetes and Hypoglycemia, run by University of Minnesota 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 8 inclusion and 38 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 2 Aug 2012. 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 combined 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.

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?

Safety, tolerability, immune activity, and pharmacokinetics of hOKT3γ1 (Ala-Ala) antibody induction therapy for the prevention of autoimmune destruction and rejection of allogeneic islet transplants as measured by:. The study lists 7 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 NCT00285194, which also lists 1 linked publication.

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 2 Aug 2012.

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