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Insulin Resistance and Statin Treatment in Renal Transplant Recipients and Patients with Chronic Kidney Disease

Phase 1
Conditions
Insulin resistance
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
Registration Number
CTIS2022-501068-16-00
Lead Sponsor
Aarhus University Hospital
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
30
Inclusion Criteria

STUDY 1: 1) Age 40-70 years; 2) BMI 20-30 kg/m2; 3) Renal transplantation > 6 months prior to inclusion; 4) Combination immunosuppressive treatment with mycophenolate, tacrolimus, and prednisolone; 5) eGFR > 29 ml/min; 6) Written, informed consent prior to study inclusion, STUDY 2: 1) Age 40-70 years; 2) BMI 20-30 kg/m2; 3) Chronic kidney disease stage 3 i.e., eGFR > 29 ml/min and < 60 ml/min; 4) Written, informed consent prior to study inclusion

Exclusion Criteria

STUDY 1: 1) Pre-existing diabetes mellitus; 2) Clinic blood pressure > 160/100 mmHg; 3) Regular treatment with doses of prednisolone > 5 mg daily; 4) Treatment with prednisolone > 15 mg/day for > 5 days, for any reason within 3 months prior to inclusion; 5) Average change in eGFR of > 5 mL/min estimated over 3 months prior to screening; 6) Blood tacrolimus level continuously outside target range; 7) Known allergy towards study medication; 8) Treatment with any type of statin as secondary prophylaxis following a cardiovascular event; 9) Prior, severe reaction to or severe side effect from any type of statin; 10) Active or chronic liver disease with serum concentration of ALAT > thrice the upper limit of normal (ULN), or spontaneous INR > 1,5; 11) Pre-existing myositis; 12) Plasma CK concentration > 4 times the ULN; 13) Hereditary galactose intolerance or known glucose/galactose malabsorption; 14) Any other organ transplantation prior to or during the trial; 15) Pregnancy or breastfeeding or unable or unwilling to use secure contraception to avoid pregnancy (female participants only); 16) Inability to understand the spoken and written information given and/or inability to give informed consent; 17) Being under legal guardianship, STUDY 2: 1) Pre-existing diabetes mellitus; 2) Clinic blood pressure > 160/100 mmHg; 3) Treatment with antidiabetic medication, other than SGLT2-inhibitors for cardio- or renal protective purposes only, and GLP-1 analogs for weight reduction purposes only; 4) Treatment with glucocorticoids or other immunosuppressive medication of any kind; 5) Known allergy towards study medication; 6) Treatment with any type of statin as secondary prophylaxis following a cardiovascular event; 7) Prior, severe reaction to or severe side effect from any type of statin; 8) Active or chronic liver disease with serum concentration of ALAT > thrice the ULN, or spontaneous INR > 1,5; 9) Pre-existing myositis from any cause; 10) Plasma CK concentration > 4 times the ULN; 11) Hereditary galactose intolerance or known glucose/galactose malabsorption; 12) Any organ transplantation prior to or during the trial; 13) Pregnancy or breastfeeding or unable or unwilling to use secure contraception to avoid pregnancy (female participants only); 14) Inability to understand the spoken and written information given and/or inability to give informed consent; 15) Being under legal guardianship

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To assess the effect of Pravastatin on insulin sensitivity compared to placebo.;Secondary Objective: To evaluate the effect of Pravastatin on insulin secretion, hormone levels and apllicability of surroate indices for insulin sensitivity, Assess the effect of Pravastatin on insulin signalling pathways on the level of gene and protein expression, Assess changes in faecal microbiota composition following treatment with Pravastatin;Primary end point(s): Insulin sensitivity assessed by hyperinsulinemic euglycemic glucose clamp
Secondary Outcome Measures
NameTimeMethod
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