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
Overview
- Phase
- Phase 4
- Intervention
- Hydrocortisone
- Conditions
- Adrenal Insufficiency
- Sponsor
- University Medical Center Groningen
- Enrollment
- 63
- Locations
- 1
- Primary Endpoint
- 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.
- Status
- Completed
- Last Updated
- 11 years ago
Overview
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.
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.
Investigators
A.P. van Beek, MD PhD
Principal Investigator
University Medical Center Groningen
Eligibility 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
Arms & Interventions
First low dose HC followed by high dose HC
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
Intervention: Hydrocortisone
First high dose HC followed by low dose HC
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
Intervention: Hydrocortisone
Outcomes
Primary Outcomes
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).
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.
Secondary Outcomes
- 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).)