NCT00766909

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
18

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Mar 2008

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2008

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

October 3, 2008

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 6, 2008

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2010

Completed
1.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2011

Completed
Last Updated

November 8, 2011

Status Verified

November 1, 2011

Enrollment Period

2.3 years

First QC Date

October 3, 2008

Last Update Submit

November 7, 2011

Conditions

Complications of Transplanted Organs and TissueDiabetes Mellitus Nos New Onset

Keywords

Insulin pulsatilityInsulin secretionInsulin sensitivityCalcineurin inhibitorCyclosporineTacrolimus

Outcome Measures

Primary Outcomes (1)

  • Insulin Sensitivity

    Serial measurements during 120 minute Hyperinsulinemic euglycemic clamp investigation. Performed 3 times on 3 individual days within 4 months after inclusion

Secondary Outcomes (9)

  • insulin secretion

    Serial measurements during IVGTT. Performed 3 times on 3 individual days within 4 months after inclusion.

  • serum free fatty acids

    Serial measurements during 5-hour infusions of CsA, Tac or saline. Performed 3 times on 3 individual days within 4 months after inclusion.

  • serum C-peptide

    erial measurements during 5-hour infusions of CsA, Tac or saline. Performed 3 times on 3 individual days within 4 months after inclusion.

  • blood cyclosporine

    erial measurements during 5-hour infusions of CsA, Tac or saline. Performed 3 times on 3 individual days within 4 months after inclusion.

  • blood tacrolimus

    Serial measurements during 5-hour infusions of CsA, Tac or saline. Performed 3 times on 3 individual days within 4 months after inclusion.

  • +4 more secondary outcomes

Study Arms (3)

CsA

EXPERIMENTAL

Cyclosporine

Drug: cyclosporine

Tac

EXPERIMENTAL

Tacrolimus

Drug: tacrolimus

Placebo

PLACEBO COMPARATOR

placebo/saline

Other: Capsules and isotonic saline

Interventions

cyclosporineDRUG

For Healthy volunteers (study 1) and Dialysis patients (study 2): Single intravenous infusion of 0.155 mg/kg over a maximum duration of 5 hours. For Dialysis Patients (study 2): Oral intake of 4 mg/kg 2 times daily for 8-11 days.

Also known as: Sandimmun
CsA
tacrolimusDRUG

For Healthy volunteers (study 1) and Dialysis patients (study 2): Single intravenous infusion of 0.0012 mg/kg over a maximum duration of 5 hours. For Dialysis Patients (study 2): Oral intake of 0.1 mg/kg 2 times daily for 8-11 days.

Also known as: Prograf
Tac
Capsules and isotonic salineOTHER

For Healthy volunteers (study 1) and Dialysis patients (study 2): Single intravenous infusion of 0.06 ml/kg isotonic saline over a maximum duration of 5 hours. For Dialysis patients (study 2): Placebo capsules 2 times daily for 8-11 days.

Also known as: Saline, NaCl
Placebo

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Healthy volunteers (Study 1):
  • Men.
  • Age between 18 years and 50 years. Upper limit can be +2 years if approved by main investigator.
  • Normal OGTT (0 and 120 min test).
  • Body mass index (BMI) 20 - 30 kg/m2. Allowed variations are 5% from the upper and lower limit.
  • 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.
  • Normal urine stix
  • Written consent to participate.
  • Hemodialysis Patients (study 2):
  • Age between 18 years and 70 years. Upper limit can be +2 years if approved by main investigator.
  • BMI \< 30 kg/m2. Allowed variations are 5% over the upper limit.
  • On the waiting-list for a kidney transplant.
  • Haemodialysis candidate.
  • Anti-conceptive treatment (contraceptive pill/intrauterine device/patch/ring/ implant/injectable contraceptive) if the patient is a fertile woman.
  • Written consent to participate. -

You may not qualify if:

  • Healthy volunteers (Study 1):
  • Anaemia with haemoglobin levels \< 7 mmol/L
  • Participation in any other clinical trial.
  • Subjects who cannot adhere to test conditions.
  • Anamnesis of clinically significant disease, such as:
  • liver disease
  • kidney disease,
  • neurological disease
  • gastrointestinal disease
  • haematological disease
  • endocrine disease
  • lung disease
  • cardiac disease
  • Drug or alcohol abuse, which would render the subject unfit according to the main investigator.
  • Blood donation 1 month prior to the study day
  • +18 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Nephrology, Aarhus University Hospital, Skejby

Aarhus, Jutland, 8200, Denmark

Location

Related Publications (2)

  • Ozbay LA, Stubbe J, Jespersen B, Jensen BL. The effects of calcineurin inhibitors on prostanoid synthesis: a randomized cross-over study in healthy humans. Transpl Int. 2013 Feb;26(2):131-7. doi: 10.1111/tri.12004. Epub 2012 Nov 29.

    PMID: 23190385DERIVED

  • Ozbay LA, Moller N, Juhl C, Bjerre M, Carstens J, Rungby J, Jorgensen KA. The impact of calcineurin inhibitors on insulin sensitivity and insulin secretion: a randomized crossover trial in uraemic patients. Diabet Med. 2012 Dec;29(12):e440-4. doi: 10.1111/dme.12028.

    PMID: 23003106DERIVED

MeSH Terms

Conditions

Insulin Resistance

Interventions

CyclosporineTacrolimusSodium Chloride

Condition Hierarchy (Ancestors)

HyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

CyclosporinsPeptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsPeptidesAmino Acids, Peptides, and ProteinsMacrolidesLactonesOrganic ChemicalsChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Study Officials

  • Lara Aygen Øzbay, MD

    Aarhus University Hospital Skejby

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 3, 2008

First Posted

October 6, 2008

Study Start

March 1, 2008

Primary Completion

June 1, 2010

Study Completion

November 1, 2011

Last Updated

November 8, 2011

Record last verified: 2011-11

Locations

DK(1)