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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

6 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-04-30

Study Completion Date

2004-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Type 1 Diabetes Hypoglycemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Allogeneic Islets of Langerhans

Intervention Type DRUG

hOKT3γ1 (Ala-Ala)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Primary islet allotransplant
2. 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:

1. Metabolic lability/instability;
2. Reduced awareness of hypoglycemia;
3. Persistently poor glucose control (as defined by HgbA1c\>10% at the end of six months of intensive management efforts with the diabetes care team);
4. Progressive secondary complications.
3. Age 18 and older
4. Able to give written informed consent

Exclusion Criteria

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

Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bernhard J. Hering, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

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Universtiy of Minnesota

Minneapolis, Minnesota, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT

PMID: 14961992 (View on PubMed)

Other Identifiers

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0003M44181

Identifier Type: -

Identifier Source: org_study_id