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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
A.P. van Beek, MD PhD, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT01546922
First received: February 7, 2012
Last updated: March 1, 2013
Last verified: March 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Adrenal Insufficiency
 Drug: Hydrocortisone
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Double Blind Cross-over Study of the Effects of Low Dose and High Dose Hydrocortisone Replacement Therapy on Cognition, Quality of Life, Metabolic Profile and Somatosensation in Patients With Secondary Adrenal Insufficiency

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • 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. [ Time Frame: 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). ] [ Designated as safety issue: No ]

    Cognitive domains to be tested: memory, executive functioning, attention and social cognition.

    The psychological tests consist of oral and written questions or computer tasks.



Secondary Outcome Measures:
  • 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. [ Time Frame: 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). ] [ Designated as safety issue: No ]
    Quality of life questionnaires have to be filled in by the participant at his/her home place and have to be returned by post.

  • 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. [ Time Frame: 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). ] [ Designated as safety issue: No ]
    Cardiovascular and metabolic risk factors, (pituitary) hormones and bone markers.

  • 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. [ Time Frame: 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). ] [ Designated as safety issue: No ]
    Measures of somatosensation: the mechanical detection threshold, the mechanical pain threshold, mechanical pain sensitivity, dynamic mechanical allodynia, wind up ratio and the pressure pain threshold.

  • 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. [ Time Frame: 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). ] [ Designated as safety issue: No ]
    The patients report common somatic complaints by filling in structured daily diaries.


Estimated Enrollment: 66
Study Start Date: February 2012
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: high hydrocortisone (HC) condition
High dose HC = 0.4-0.6 mg/kg body weight
 Drug: Hydrocortisone
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.
Active Comparator: low hydrocortisone (HC) condition
Low dose HC = 0.2-0.3 mg/kg body weight
 Drug: Hydrocortisone
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.

Detailed Description:
  • Rationale: A wide variety in hydrocortisone (HC) substitution dose-regimens are considered physiological for patients with adrenal insufficiency. However, it is likely that cognition is negatively influenced by higher cortisol exposure to the brain. No studies have been performed to assess the effects of treatment regimens with a low physiological HC substitution dose on cognition in comparison to a high physiological HC substitution dose. These treatment regimens should take body weight and multiple dosing into account. In addition, substitution doses should be monitored by clinical evaluation and biochemical analysis for adverse effects associated with over- or under-replacement.
  • Intervention: Patients with secondary adrenal insufficiency will be randomized in two groups to 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. At baseline and after both treatment periods, patients will be tested.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01546922

Locations
Netherlands
University Medical Centre Groningen
Groningen, Netherlands, 9700RB
Sponsors and Collaborators
University Medical Centre Groningen
Investigators
Principal Investigator: André P van Beek, Dr. University Medical Centre Groningen
  More Information

No publications provided

Responsible Party: A.P. van Beek, MD PhD, Principal Investigator, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT01546922     History of Changes
Other Study ID Numbers: NL 35668.042.11, 2011-000864-82
Study First Received: February 7, 2012
Last Updated: March 1, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: Dutch Health Care Inspectorate

Keywords provided by University Medical Centre Groningen:
Hydrocortisone
Cognition
Adrenal insufficiency
Quality of Life
 Common Somatic Complaints
Cardiovascular/Metabolic Profile
Somatosensation

Additional relevant MeSH terms:
Addison Disease
Adrenal Insufficiency
Adrenal Gland Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Cortisol succinate
Hydrocortisone acetate
 Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone
Hydrocortisone-17-butyrate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents

ClinicalTrials.gov processed this record on May 22, 2013