Prevalence of Adrenal Insufficiency in Kidney Transplanted Patients in Glucocorticoid Treatment

• ClinicalTrials.gov Identifier: NCT03136562
• Recruitment Status: Unknown
• First Posted: May 2, 2017
• Last Update Posted: May 5, 2017
• Sponsor: Rigshospitalet, Denmark
• Information provided by (Responsible Party): Ulla Feldt-Rasmussen, Rigshospitalet, Denmark

Tracking Information

• First Submitted Date: February 21, 2017
• First Posted Date: May 2, 2017
• Last Update Posted Date: May 5, 2017
• Actual Study Start Date: March 20, 2017
• Estimated Primary Completion Date: February 1, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 2, 2017)

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. ]

Cutoff for normal adrenal function: 30 min p-cortisol >/= 420 nmol/L.

Original Primary Outcome Measures (submitted: April 26, 2017)

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. ]

Cutoff for normal adrenal function: 30 min p-cortisol >/= 420 nmol/L.

Current Secondary Outcome Measures (submitted: May 2, 2017)

• 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 Measures (submitted: April 26, 2017)

• 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Prevalence of Adrenal Insufficiency in Kidney Transplanted Patients in Glucocorticoid Treatment
• 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 Description

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.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Cross-Sectional
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Whole blood and saliva.

• Sampling Method: Non-Probability Sample
• Study Population: 30 kidney transplanted patients and 30 patients in dialysis.
• Condition: Adrenal Insufficiency

Intervention

Diagnostic Test: Synacthen test

250 microg synacthen test performed fasting, in the morning. P-cortisol measured before and 30 minutes after Synacthen injection.

Study Groups/Cohorts

• Kidney transplanted patients
  Kidney transplanted patients in prednisolone treatment. Adrenal function is assessed by a synacthen test.
  Intervention: Diagnostic Test: Synacthen test
• Control group
  Patients in dialysis not in prednisolone treatment. Adrenal function is assessed by a synacthen test.
  Intervention: Diagnostic Test: Synacthen test

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: April 26, 2017): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 1, 2019
• Estimated Primary Completion Date: February 1, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adult patients (>18 years).
• Kidney transplated patients or patients with kidney failure treated in dialysis.
• Prednisone min 5 mg/day max 7,5 mg/day for the kidney transplanted patients (control group not treated with prednisone).

Exclusion Criteria:

• Other major organ disease.
• Anemia with hemoglobin level less than 6,5 mmol/L.
• Not willing to pause any oestrogen tratment for a minimum of 6 weeks.
• Pregnancy.
• Not understanding Danish language or otherwise not able to provide a written informed concent.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Not Provided
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark

Administrative Information

• NCT Number: NCT03136562
• Other Study ID Numbers: NTx-CSI
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Ulla Feldt-Rasmussen, Rigshospitalet, Denmark
• Study Sponsor: Rigshospitalet, Denmark
• Collaborators: Not Provided

Investigators

• Principal Investigator: Ulla Feldt-Rasmussen, Professor; Department of Endocrinology, Rigshospitalet

• PRS Account: Rigshospitalet, Denmark
• Verification Date: May 2017