Clinical Trial: Prevalence of Adrenal Insufficiency in Kidney Transplanted Patients in Glucocorticoid Treatment

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Prevalence of Adrenal Insufficiency in Kidney Transplanted Patients (NTx) in Glucocorticoid Treatment

Brief Summary:

The primary purpose of this study is to determine the prevalence of adrenal insufficiency in a population of patients with kidney transplants receiving low dose prednisone treatment.

Development of glucocorticoid-induced adrenal insufficiency is a serious adverse effect to glucocorticoid treatment. The study includes a control group of patients with kidney failure currently treated in dialysis, who are not in glucocorticoid treatment.

Individual genotyping is performed to determine the haplotype of glucocorticoid receptor polymorphisms: N363 S, BclI, ER23/23EK and 9β in all the patients with the purpose of investigating this as a risk factor for the development of adrenal insufficiency. The hypothesis is that subjects with one or another of the polymorphisms in the glucocorticoid receptor gene will either have increased or diminished glucocorticoid sensitivity.

Using validated questionnaires assessing the quality of life and functional level of the patients enrolled in the study we aim to establish a link between functional level and biochemically proven adrenal insufficiency.

Other secondary outcomes in the study includes bloodpressure, body composition, bone density, metabolic syndrome, inflammation and salivary cortisol profiles.

Detailed Summary:

Adrenal function is assessed in 30 prednisolon treated kidney transplanted patients and compared with 30 patients in dialysis, who are not treated with glucocorticoids. Adrenal function is evaluated using a 250µg Synacthen® test, performed fasting, in the morning, 48 h after the last prednisolone dose.

Cut-off for normal adrenal function is locally validated assay specific cut-off of 30 min P-cortisol >420 nmol/l. The primary outcome measure of this study is P-cortisol concentrations 30 minutes after Synacthen® injection in prednisolone treated patients compared with comtrols. Secondary, 30 minutes P-cortisol is examined in relation to glucocorticoid receptor haplotypes.

The genotyping is determined using polymerase chain reaction (PCR).

The questionnaires used in this study includes EQ-5D, SF-36, Patient Life Situation Form, CushingQol and ADDOQol.

Sponsor: Rigshospitalet, Denmark

Current Primary Outcome: The primary outcome measure of this study is the result of the Synacthen® test using primarily the level of P-cortisol 30 minutes after the injection of synacthen. [ Time Frame: The time frame of each Synacthen® test is approximately 90 minutes. ]

Original Primary Outcome: The primary outcome measure of this study is the result of the Synacthen® test using primarily the level of P-cortisol 30 minutes after the injection of synacthen. [ Time Frame: At the study visit. ]

Current Secondary Outcome:

• Registration of history of treatment. [ Time Frame: The registration will take place at the study visit (approximately 90 minutes). ]
  History of treatment with prednisone and other types of glucocorticoids to examine dosage and time of treatment as risk factors.
• Quality of life and functional level. [ Time Frame: Patients receive and fill out the questionnaires prior to their arrival at the study visit and hand them in after the Synacthen® test. Patients receive questionnaires either by mail or at one of their visits in the out patient clinic. ]
  Assessed in all patients enrolled in the study using validated questionnaires as a means to establish a link between functional level and biochemically proven adrenal insufficiency.
• Determination of the specific type of glucocorticoid receptor using genotyping in all the patients with the purpose of investigating this as a risk factor for the development of adrenal insufficiency. [ Time Frame: Blood for genotyping is sampled from each patient at the study visit during the Synacthen® test. The blood samples are stored frozen and analyzed concurrently. ]
  Patients are genotyped for 4 polymorphisms (9 beta, ER22/23EK, Bcl1 and N363S) of the glucocorticoid receptor.
• Body composition [ Time Frame: After the Synacthen® test the height, weight, waist and hip circumference are measured at the study visit. ]
  Height, weight, waist and hip circumference.
• Bone density. [ Time Frame: The results from latest Dxa-scan performed in rutine settings are collected from the patients on the same day as the Synacthen® test. ]
  Results from Dxa-scan.
• Metabolic syndrome. [ Time Frame: The waistline and blood pressure are measured at the study visit after the Synacthen® test. The blood samples are collected as part of the test and analyazed on the same day. ]
  Waistline, triglyceride level, HDL cholesterol level, blood pressure and fasting blood sugar is assessed in all the patients.
• Salivary cortisol profiles. [ Time Frame: Saliva is sampled from each patient at the study visit as part of the Synacthen® test. The samples are stored frozen and analyzed concurrently after all 60 Synacthen® tests have been performed. ]
  Cortisol concentration in saliva.

Original Secondary Outcome:

• Registration of history of treatment. [ Time Frame: At the study visit. ]
  History of treatment with prednisone and other types of glucocorticoids to examine dosage and time of treatment as risk factors.
• Quality of life and functional level. [ Time Frame: At the study visit. ]
  Assessed in all patients enrolled in the study using validated questionnaires as a means to establish a link between functional level and biochemically proven adrenal insufficiency.
• Determination of the specific type of glucocorticoid receptor using genotyping in all the patients with the purpose of investigating this as a risk factor for the development of adrenal insufficiency. [ Time Frame: At the study visit. ]
  Patients are genotyped for 4 polymorphisms (9 beta, ER22/23EK, Bcl1 and N363S) of the glucocorticoid receptor.
• Body composition [ Time Frame: At the study visit. ]
  Height, weight, waist and hip circumference.
• Bone density. [ Time Frame: The latest Dxa-scan performed in rutine settings. ]
  Results from Dxa-scan.
• Metabolic syndrome. [ Time Frame: At the study visit. ]
  Waistline, triglyceride level, HDL cholesterol level, blood pressure and fasting blood sugar is assessed in all the patients.
• Salivary cortisol profiles. [ Time Frame: At the study visit. ]
  Cortisol concentration in saliva.

Information By: Rigshospitalet, Denmark

Dates:
Date Received: February 21, 2017
Date Started: March 20, 2017
Date Completion: June 1, 2019
Last Updated: May 2, 2017
Last Verified: May 2017