Rosiglitazone and Insulin Resistance in Renally Impaired Patients

This study has been terminated.
(it was not possible to recruit new patients anymore)
Sponsor:
Information provided by:
Leiden University Medical Center
ClinicalTrials.gov Identifier:
NCT00452166
First received: March 26, 2007
Last updated: September 30, 2008
Last verified: September 2008
  Purpose

30 non-diabetic, non-obese patients with stage 4 chronic kidney disease will be asked to participate in this metabolic study.

The primary aim of this study is to determine the effect of rosiglitazone on insulin resistance in non-obese patients with non-diabetic stage 4 CKD.

Secondary end points are the effects on inflammation (hsCRP), lipid profile, bone density and body composition.


Condition Intervention Phase
Chronic Kidney Disease
Insulin Resistance
Drug: rosiglitazone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Rosiglitazone and Insulin Resistance in Renally Impaired Patients

Resource links provided by NLM:


Further study details as provided by Leiden University Medical Center:

Primary Outcome Measures:
  • Insulin sensitivity [ Time Frame: 12 weeks ]

Secondary Outcome Measures:
  • inflammation [ Time Frame: 12 weeks ]
  • lipid profile [ Time Frame: 12 weeks ]
  • bone density [ Time Frame: 12 weeks ]
  • body composition [ Time Frame: 12 weeks ]

Estimated Enrollment: 30
Study Start Date: April 2007
Study Completion Date: May 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Detailed Description:

This part of the study will be performed in 30 non-diabetic non-obese patients. In this study patients will receive single-dose oral placebo and rosiglitazone once daily to be taken in the morning. During the first 8 weeks the patients will be dosed with 4 mg rosiglitazone. Then the concentration of the serum transaminases will be checked and if these are within an acceptable range, the doses will be doubled for the remainder of the study. If the changes in serum transaminases are considered clinically significant the patient will be withdrawn from the study and if the transaminases have increased but not to clinically significant level then the treatment of patient may be continued on the 4 mg daily dose.

The insulin sensitivity will be measured by using a euglycaemic hyperinsulinaemic clamp technique, which is validated technique.

Screening of eligible patients: fasting glucose ≤ 7,0 mmol/L and BMI ≤ 30.

Exclusion criteria are:

  • A diagnosis of diabetes mellitus for which the patient uses insulin;
  • Significant co-morbidities which, according to the treating nephrologists, makes it unlikely that the patient will be able to complete the foreseen study period;
  • Significant cardiovascular co-morbidities which are likely to interfere with the objectives of the study (morbid obesity, family history of dyslipidemia, etc.); at the discretion of the treating nephrologists or the principal investigator;
  • Allergy for PPAR's;
  • Cardiac disease with marked limitation of functional capacity (New York Heart Association III or IV clinical status);
  • Use of immunosuppressant agents;
  • History of renal transplant;
  • Hepatic insufficiency (defined as transaminase concentrations above > 2.5 times the upper limit of normal for the laboratories);
  • A history of alcohol abuse or excessive alcohol use defined as more than 21 consumptions per week;
  • For female patients: pregnancy, the intention to become pregnant within the study period, or lactating patients Eligible patients will receive insulin (Actrapid; Novo Nordisk A/S, Copenhagen, Denmark) at an infusion rate of 40 mU (288 pmol)/kg/m2 body surface area per minute. Euglycemia (target blood concentration of 5 mM) will be maintained by adjusting the rate of 20% glucose infusion according to whole blood glucose concentration measured from arterialized venous blood; the patient keeps his or her right arm in a box containing heated air (60°C). Insulin and glucose will be infused in the left arm. In healthy subjects, hepatic glucose production is completely suppressed when the serum insulin level is >60 mU/L. Here the expected insulin level in serum is 80 mU/L. Blood samples will be drawn at 5 min intervals for the determination of blood glucose, and at 10 min intervals during the period of 90 -120 min for the determination of serum insulin and free fatty acids. The insulin-sensitivity index (ISI) will be calculated by dividing the average glucose-infusion rate by the mean steady-state serum insulin levels during a period of 90 -120 min. In addition to glucose-infusion rate and insulin sensitivity index, the influence of the clamp on levels of FFA will also be assed.

At baseline and during the follow-up of the study inflammatory parameters (hsCRP) and lipids will be measured. At baseline and at the end a bone densitometry (DEXA) will be performed.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • CKD stage 4
  • BMI ≤ 30
  • Fasting glucose < 7 mmol/l

Exclusion Criteria:

Exclusion of patients will take place in case of:

  • A diagnosis of diabetes mellitus for which the patient uses insulin
  • Significant co-morbidities which, according to the treating nephrologists, makes it unlikely that the patient will be able to complete the foreseen study period
  • Significant cardiovascular co-morbidities which are likely to interfere with the objectives of the study (morbid obesity, family history of dyslipidemia, etc.); at the discretion of the treating nephrologists or the principal investigator
  • Allergy for PPAR's
  • Cardiac disease with marked limitation of functional capacity (New York Heart Association III or IV clinical status)
  • Use of immunosuppressant agents
  • History of renal transplant
  • Hepatic insufficiency (defined as transaminase concentrations above > 2.5 times the upper limit of normal for the laboratories)
  • A history of alcohol abuse or excessive alcohol use defined as more than 21 consumptions per week
  • For female patients: pregnancy, the intention to become pregnant within the study period, or lactating patients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00452166

Locations
Netherlands
LUMC
Leiden, Netherlands
Sponsors and Collaborators
Leiden University Medical Center
Investigators
Principal Investigator: andre gaasbeek, md LUMC leiden
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00452166     History of Changes
Other Study ID Numbers: p06-108a
Study First Received: March 26, 2007
Last Updated: September 30, 2008
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Insulin Resistance
Kidney Diseases
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Urologic Diseases
Renal Insufficiency
Rosiglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014