Diabetogenicity of Cyclosporine and Tacrolimus

• Status: Completed
• Trial end date: 2011-11-01
• Target enrollment: 0
• Participant gender: All

Summary

Cyclosporine (CsA) and Tacrolimus (Tac) are immunosuppressive agents comprising the cornerstone of treatment among organ transplant recipients. Unfortunately diabetes is a known complication after transplantation, yet the underlying mechanisms of this type of diabetes are still unresolved. A direct comparison of the diabetogenic effects of CsA and Tac, without interference of corticosteroid treatment, has not yet been investigated using a hyperinsulinemic euglycemic glucose clamp technique, which is the best method for estimating insulin sensitivity.

Randomized, investigator-blinded cross-over studies will be carried out, studying 10 healthy subjects and 10 hemodialysis patients. Each participant will receive treatment with CsA, Tac and placebo respectively in a random order. The results will be of relevance to the choice and monitoring of immunosuppressive regimens in kidney transplant recipients as well as the development of better treatment modalities for diabetes.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Aarhus
• Treatments: Cyclosporine; Cyclosporins; Tacrolimus

Criteria

Inclusion Criteria:

Healthy volunteers (Study 1):

1. Men.

2. Age between 18 years and 50 years. Upper limit can be +2 years if approved by main investigator.

3. Normal OGTT (0 and 120 min test).

4. Body mass index (BMI) 20 - 30 kg/m2. Allowed variations are 5% from the upper and lower limit.

5. Normal serum creatinine and ionisized calcium. Allowed variations are 20% from the upper and lower limit of the normal value for creatinine and 5% for calcium.

6. Normal urine stix

7. Written consent to participate.

Hemodialysis Patients (study 2):

1. Age between 18 years and 70 years. Upper limit can be +2 years if approved by main investigator.

2. BMI < 30 kg/m2. Allowed variations are 5% over the upper limit.

3. On the waiting-list for a kidney transplant.

4. Haemodialysis candidate.

5. Anti-conceptive treatment (contraceptive pill/intrauterine device/patch/ring/ implant/injectable contraceptive) if the patient is a fertile woman.

6. Written consent to participate. -

Exclusion Criteria:

Healthy volunteers (Study 1):

1. Anaemia with haemoglobin levels < 7 mmol/L

2. Participation in any other clinical trial.

3. Subjects who cannot adhere to test conditions.

4. Anamnesis of clinically significant disease, such as:

• liver disease

• kidney disease,

• neurological disease

• gastrointestinal disease

• haematological disease

• endocrine disease

• lung disease

• cardiac disease

5. Drug or alcohol abuse, which would render the subject unfit according to the main investigator.

6. Blood donation 1 month prior to the study day

7. Patients with established allergy against CI or other medical products, which might pose a risk if they participated in this study.

8. Use of prescription drugs within one month prior to the study days, unless they are clinically insignificant according to the main investigator.

9. Smoking 8 hours prior to the study day

10. Vigorous exercise 30 minutes prior to the study day.

Hemodialysis Patients (study 2):

1. Peritoneal dialysis.

2. Anaemia with haemoglobin levels < 6 mmol/L.

3. Participation in any other clinical trial.

4. Treatment with corticosteroids, CsA or Tac.

5. Patients who cannot adhere to test conditions.

6. Patients with established allergy against CI or other medical product, which might pose a risk if they participated in this study.

7. Drug or alcohol abuse, which would render the subject unfit according to the main investigator.

8. Anamnesis of current diabetes and/or intake of anti-diabetic medication.

9. Malignancy.

10. Uncontrolled infection.

11. Uncontrolled hypertension.

12. Smoking 8 hours prior to the study day.

13. Vigorous exercise 30 minutes prior to the study day

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