Hydrocortisone Replacement in Patients With Secondary Adrenal Insufficiency (SUPREME CORT)

NCT01546922 | Completed Phase 4 Results

• 2 other identifiers: NL 35668.042.112011-000864-82
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to investigate whether a physiologically low hydrocortisone (HC) dose is better for cognition as compared to a physiologically high HC dose. In addition, quality of life, metabolic profile and somatosensation will be described in relation to HC dose.

Conditions

Adrenal Insufficiency

Keywords

Hydrocortisone; Cognition; Adrenal insufficiency; Quality of Life; Common Somatic Complaints; Cardiovascular/Metabolic Profile; Somatosensation

Outcome Measures

Primary Outcomes (1)

• Change in Cognition After 10 Weeks of Treatment With a Low Dose of Hydrocortisone Compared to 10 Weeks of Treatment With a High Dose of Hydrocortisone.

  Cognitive domains to be tested: memory, executive functioning, attention and social cognition. The psychological tests consist of oral and written questions or computer tasks. Data is given as Z-scores based on normative data. Higher Z-scores represent a better performance.

  After completion of treatment period 1 (that is after 10 weeks from baseline) and after treatment period 2 (that is after 20 weeks from baseline).

Secondary Outcomes (4)

• Change in Quality of Life After 10 Weeks of Treatment With a Low Dose of Hydrocortisone Compared to 10 Weeks of Treatment With a High Dose of Hydrocortisone.

  After completion of treatment period 1 (that is after 10 weeks from baseline) and after treatment period 2 (that is after 20 weeks from baseline).

• Change in Metabolic Profile After 10 Weeks of Treatment With a Low Dose of Hydrocortisone Compared to 10 Weeks of Treatment With a High Dose of Hydrocortisone.

  After completion of treatment period 1 (that is after 10 weeks from baseline) and after treatment period 2 (that is after 20 weeks from baseline).

• Change in Somatosensation After 10 Weeks of Treatment With a Low Dose of Hydrocortisone Compared to 10 Weeks of Treatment With a High Dose of Hydrocortisone.

  After completion of treatment period 1 (that is after 10 weeks from baseline) and after treatment period 2 (that is after 20 weeks from baseline).

• Change in Perceived Common Somatic Complaints After 10 Weeks of Treatment With a Low Dose of Hydrocortisone Compared to 10 Weeks of Treatment With a High Dose of Hydrocortisone.

  during treatment period 1 (that is from week 1 to week 10 from baseline) and during treatment period 2 (that is from week 11 to week 20 from baseline).

Study Arms (2)

First low dose HC followed by high dose HC

ACTIVE COMPARATOR

First low dose of hydrocortisone = 0.2-0.3 mg/kg body weight for 10 weeks followed by a high dose of hydrocortisone = 0.4-0.6 mg/kg body weight

Drug: Hydrocortisone

First high dose HC followed by low dose HC

ACTIVE COMPARATOR

First a high dose of hydrocortisone = 0.4-0.6 mg/kg body weight for 10 weeks followed by a low dose of hydrocortisone = 0.2-0.3 mg/kg body weight

Drug: Hydrocortisone

Interventions

Hydrocortisone DRUG

Patients receive either a low dose HC (0.2-0.3 mg/kg body weight) for 10 weeks followed by 10 weeks of high dose HC (0.4-0.6 mg/kg body weight) or vice versa.

First high dose HC followed by low dose HC; First low dose HC followed by high dose HC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with secondary adrenal insufficiency.
• Age ≥ 18 - 75 years
• ≥ One year after tumor treatment with surgery and/or radiotherapy
• On stable concomitant medications for at least six months prior to entry of study
• Body weight 50-100 kg

You may not qualify if:

• Inability of legal consent
• Documented cognitive impairment
• Drug abuse/dependence
• History of / current psychiatric disorders
• Use of anti-epileptics (e.g. carbamezapine)
• Cushing Disease
• Type 1 diabetes or Type 2 diabetes with medication known to induce hypoglycemia (f.e. Sulfonylurea derivatives
• Current treatment for second malignancy
• Have a significant medical condition (e.g. hepatic, respiratory, or cardiovascular) which, in the opinion of the investigator, may interfere with the interpretation of results and safety or efficacy evaluations.
• A history of frequent hypocortisolism
• Hospitalization during study
• Work in shifts

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Centre Groningen

Groningen, Provincie Groningen, 9700RB, Netherlands

Location

Related Publications (5)

• Sorgdrager FJH, Werumeus Buning J, Bos EH, Van Beek AP, Kema IP. Hydrocortisone Affects Fatigue and Physical Functioning Through Metabolism of Tryptophan: A Randomized Controlled Trial. J Clin Endocrinol Metab. 2018 Sep 1;103(9):3411-3419. doi: 10.1210/jc.2018-00582.

  PMID: 29982583 DERIVED

• Werumeus Buning J, Touw DJ, Brummelman P, Dullaart RPF, van den Berg G, van der Klauw MM, Kamp J, Wolffenbuttel BHR, van Beek AP. Pharmacokinetics of oral hydrocortisone - Results and implications from a randomized controlled trial. Metabolism. 2017 Jun;71:7-16. doi: 10.1016/j.metabol.2017.02.005. Epub 2017 Feb 13.

  PMID: 28521880 DERIVED

• Werumeus Buning J, van Faassen M, Brummelman P, Dullaart RP, van den Berg G, van der Klauw MM, Kerstens MN, Stegeman CA, Muller Kobold AC, Kema IP, Wolffenbuttel BH, van Beek AP. Effects of Hydrocortisone on the Regulation of Blood Pressure: Results From a Randomized Controlled Trial. J Clin Endocrinol Metab. 2016 Oct;101(10):3691-3699. doi: 10.1210/jc.2016-2216. Epub 2016 Aug 4.

  PMID: 27490921 DERIVED

• Werumeus Buning J, Brummelman P, Koerts J, Dullaart RP, van den Berg G, van der Klauw MM, Sluiter WJ, Tucha O, Wolffenbuttel BH, van Beek AP. Hydrocortisone Dose Influences Pain, Depressive Symptoms and Perceived Health in Adrenal Insufficiency: A Randomized Controlled Trial. Neuroendocrinology. 2016;103(6):771-8. doi: 10.1159/000442985. Epub 2015 Dec 9.

  PMID: 26646751 DERIVED

• Werumeus Buning J, Brummelman P, Koerts J, Dullaart RP, van den Berg G, van der Klauw MM, Tucha O, Wolffenbuttel BH, van Beek AP. The effects of two different doses of hydrocortisone on cognition in patients with secondary adrenal insufficiency--results from a randomized controlled trial. Psychoneuroendocrinology. 2015 May;55:36-47. doi: 10.1016/j.psyneuen.2015.02.001. Epub 2015 Feb 10.

  PMID: 25705800 DERIVED

MeSH Terms

Conditions

Adrenal Insufficiency

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Results Point of Contact

• Title: A. P. van Beek, MD PhD
• Organization: University Medical Center Groningen

a.p.van.beek@umcg.nl

00315036110388

Study Officials

• André P van Beek, Dr.

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 7, 2012
• First Posted: March 7, 2012
• Study Start: February 1, 2012
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: July 14, 2014
• Results First Posted: July 14, 2014

Record last verified: 2014-06

Locations

NL (1)