Adrenal Insufficiency
Conditions
Keywords
Hydrocortisone, Cognition, Adrenal insufficiency, Quality of Life, Common Somatic Complaints, Cardiovascular/Metabolic Profile, Somatosensation
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.
Interventions
DRUGHydrocortisone
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.
Sponsors
University Medical Center Groningen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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
| Measure | Time frame | Description |
|---|---|---|
| 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). | 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. | 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). | 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. | 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). | 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. | 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). | The patients report common somatic complaints by filling in structured daily diaries. |
Countries
Netherlands
Participant flow
Pre-assignment details
Sixty-three patients were included in the study. Three patients withdrew from the study during the run-in phase, therefore a total of 60 patients started the first treatment period.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants completing both study periods | 47 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Period of 10 Weeks | Investigator's judgment | 1 | 0 |
| First Period of 10 Weeks | Protocol Violation | 3 | 1 |
| First Period of 10 Weeks | Withdrawal by Subject | 1 | 1 |
| Second Period of 10 Weeks | Protocol Violation | 3 | 1 |
| Second Period of 10 Weeks | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age at diagnosis | 31 years INTER_QUARTILE_RANGE 16 |
| Age at radiotherapy | 43 years |
| Age at surgery | 39 years |
| Age, Continuous | 55 years INTER_QUARTILE_RANGE 14 |
| Body weight | 82.5 kilogram INTER_QUARTILE_RANGE 13.9 |
| Childhood onset/Adult onset Adult onset | 41 participants |
| Childhood onset/Adult onset Childhood onset | 6 participants |
| Desmopressin substitution | 9 participants |
| Dose per kg body weight prior to randomization | 0.32 mg/kg body weight |
| Duration of hydrocortisone treatment prior to randomization | 12 years |
| Growth hormone (GH) Participants substituted | 21 participants |
| Growth hormone (GH) Participants unsubstituted | 10 participants |
| Median time since radiotherapy | 12 years |
| Median time since surgery | 11 years |
| Number of daily dosings prior to randomization 1 dose per day | 3 participants |
| Number of daily dosings prior to randomization 2 doses per day | 33 participants |
| Number of daily dosings prior to randomization 3 doses per day | 11 participants |
| Number of hormonal replacements 1 hormonal replacement | 3 participants |
| Number of hormonal replacements 2 hormonal replacements | 9 participants |
| Number of hormonal replacements 3 hormonal replacements | 21 participants |
| Number of hormonal replacements 4 hormonal replacements | 11 participants |
| Number of hormonal replacements 5 hormonal replacements | 3 participants |
| Patients with a second surgery | 5 participants |
| Region of Enrollment Netherlands | 47 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 29 Participants |
| Sex hormone Men: testosterone substitution | 23 participants |
| Sex hormone Participants substituted | 27 participants |
| Sex hormone Premenopausal women: estrogen substitution | 4 participants |
| Thyroid hormone substitution | 43 participants |
| Total daily dose hydrocortisone treatment prior to randomization | 25 mg/day |
| Type of radiotherapy Cranial irradiation | 2 participants |
| Type of radiotherapy Pituitary radiotherapy | 16 participants |
| Type of radiotherapy Radiotherapy for extracranial tumors | 1 participants |
| Type of surgery Craniotomy | 9 participants |
| Type of surgery Transsphenoïdal surgery | 23 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 58 | 13 / 55 |
| serious Total, serious adverse events | 1 / 58 | 1 / 55 |
Outcome results
Primary
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.
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).
Population: The participants completing both study periods were analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose of Hydrocortisone | 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. | Divided attention - Number of omission errors | -0.02 Z-scores based on normative data. | Standard Deviation 0.86 |
| Low Dose of Hydrocortisone | 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. | 15 Words Test-Total immediate memory | 0.43 Z-scores based on normative data. | Standard Deviation 1.02 |
| Low Dose of Hydrocortisone | 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. | Divided attention - Number of commission errors | 0.30 Z-scores based on normative data. | Standard Deviation 1.01 |
| Low Dose of Hydrocortisone | 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. | 15 Words Test-Recognition | -0.11 Z-scores based on normative data. | Standard Deviation 0.88 |
| Low Dose of Hydrocortisone | 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. | Visual scanning - Reaction time for target stimuli | -0.38 Z-scores based on normative data. | Standard Deviation 1.04 |
| Low Dose of Hydrocortisone | 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. | RBMT-Delayed Memory | 0.07 Z-scores based on normative data. | Standard Deviation 0.98 |
| Low Dose of Hydrocortisone | 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. | Visual scanning - Number of omission errors | -0.03 Z-scores based on normative data. | Standard Deviation 1.06 |
| Low Dose of Hydrocortisone | 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. | Digit Span forward - Short term memory | 0.49 Z-scores based on normative data. | Standard Deviation 0.97 |
| Low Dose of Hydrocortisone | 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. | Visual scanning - Number of commission errors | -0.72 Z-scores based on normative data. | Standard Deviation 0.26 |
| Low Dose of Hydrocortisone | 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. | 15 Words Test - Learning Score | 0.08 Z-scores based on normative data. | Standard Deviation 1.05 |
| Low Dose of Hydrocortisone | 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. | Alertness - Reaction time tonic alertness | -0.90 Z-scores based on normative data. | Standard Deviation 0.73 |
| Low Dose of Hydrocortisone | 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. | Rey Complex Figure - Immediate memory | 1.14 Z-scores based on normative data. | Standard Deviation 1.26 |
| Low Dose of Hydrocortisone | 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. | Alertness - Reaction time phasic alertness | -1.03 Z-scores based on normative data. | Standard Deviation 0.67 |
| Low Dose of Hydrocortisone | 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. | 15 Words Test-Short-term memory | 0.36 Z-scores based on normative data. | Standard Deviation 1.01 |
| Low Dose of Hydrocortisone | 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. | Semantic fluency | 0.02 Z-scores based on normative data. | Standard Deviation 1.24 |
| Low Dose of Hydrocortisone | 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. | Rey Complex Figure - Delayed memory | 1.11 Z-scores based on normative data. | Standard Deviation 1.22 |
| Low Dose of Hydrocortisone | 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. | Phonemic fluency | 0.32 Z-scores based on normative data. | Standard Deviation 1.48 |
| Low Dose of Hydrocortisone | 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. | 15 Words Test - Delayed Memory | 0.02 Z-scores based on normative data. | Standard Deviation 1.04 |
| Low Dose of Hydrocortisone | 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. | Digit Span backwards-Working memory | 0.05 Z-scores based on normative data. | Standard Deviation 0.86 |
| Low Dose of Hydrocortisone | 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. | Divided attention-reaction time auditory response | -0.87 Z-scores based on normative data. | Standard Deviation 0.81 |
| Low Dose of Hydrocortisone | 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. | Trail Making Test - Time condition A | -0.32 Z-scores based on normative data. | Standard Deviation 1.14 |
| Low Dose of Hydrocortisone | 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. | RBMT-Delayed corrected for immediate memory | 0.85 Z-scores based on normative data. | Standard Deviation 1.09 |
| Low Dose of Hydrocortisone | 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. | Trail Making Test - Time condition B | 0.16 Z-scores based on normative data. | Standard Deviation 1.46 |
| Low Dose of Hydrocortisone | 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. | Divided attention-reaction time visual response | -0.06 Z-scores based on normative data. | Standard Deviation 1 |
| Low Dose of Hydrocortisone | 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. | Trail Making Test - Condition B/A | 0.37 Z-scores based on normative data. | Standard Deviation 1.42 |
| Low Dose of Hydrocortisone | 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. | 15 Words Test - Delayed corrected for total memory | -0.30 Z-scores based on normative data. | Standard Deviation 0.99 |
| Low Dose of Hydrocortisone | 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. | Social Cognition | -0.67 Z-scores based on normative data. | Standard Deviation 1.2 |
| Low Dose of Hydrocortisone | 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. | RBMT-Immediate Memory | -0.41 Z-scores based on normative data. | Standard Deviation 0.95 |
| High Dose of Hydrocortisone | 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. | Social Cognition | -0.71 Z-scores based on normative data. | Standard Deviation 1.15 |
| High Dose of Hydrocortisone | 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. | RBMT-Immediate Memory | -0.42 Z-scores based on normative data. | Standard Deviation 1.33 |
| High Dose of Hydrocortisone | 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. | RBMT-Delayed Memory | 0.10 Z-scores based on normative data. | Standard Deviation 1.33 |
| High Dose of Hydrocortisone | 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. | RBMT-Delayed corrected for immediate memory | 0.89 Z-scores based on normative data. | Standard Deviation 1.34 |
| High Dose of Hydrocortisone | 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. | 15 Words Test-Short-term memory | -0.03 Z-scores based on normative data. | Standard Deviation 1.03 |
| High Dose of Hydrocortisone | 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. | 15 Words Test-Total immediate memory | 0.25 Z-scores based on normative data. | Standard Deviation 0.92 |
| High Dose of Hydrocortisone | 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. | 15 Words Test - Learning Score | 0.38 Z-scores based on normative data. | Standard Deviation 1.19 |
| High Dose of Hydrocortisone | 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. | 15 Words Test - Delayed Memory | 0.23 Z-scores based on normative data. | Standard Deviation 0.97 |
| High Dose of Hydrocortisone | 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. | 15 Words Test - Delayed corrected for total memory | -0.16 Z-scores based on normative data. | Standard Deviation 0.99 |
| High Dose of Hydrocortisone | 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. | 15 Words Test-Recognition | 0.08 Z-scores based on normative data. | Standard Deviation 0.71 |
| High Dose of Hydrocortisone | 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. | Digit Span forward - Short term memory | 0.56 Z-scores based on normative data. | Standard Deviation 0.97 |
| High Dose of Hydrocortisone | 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. | Rey Complex Figure - Immediate memory | 1.40 Z-scores based on normative data. | Standard Deviation 1.29 |
| High Dose of Hydrocortisone | 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. | Rey Complex Figure - Delayed memory | 1.28 Z-scores based on normative data. | Standard Deviation 1.29 |
| High Dose of Hydrocortisone | 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. | Divided attention-reaction time auditory response | -0.89 Z-scores based on normative data. | Standard Deviation 0.82 |
| High Dose of Hydrocortisone | 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. | Divided attention-reaction time visual response | 0.03 Z-scores based on normative data. | Standard Deviation 0.94 |
| High Dose of Hydrocortisone | 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. | Divided attention - Number of omission errors | -0.14 Z-scores based on normative data. | Standard Deviation 0.93 |
| High Dose of Hydrocortisone | 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. | Divided attention - Number of commission errors | 0.34 Z-scores based on normative data. | Standard Deviation 0.76 |
| High Dose of Hydrocortisone | 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. | Visual scanning - Reaction time for target stimuli | -0.36 Z-scores based on normative data. | Standard Deviation 1.03 |
| High Dose of Hydrocortisone | 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. | Visual scanning - Number of omission errors | 0.08 Z-scores based on normative data. | Standard Deviation 1.08 |
| High Dose of Hydrocortisone | 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. | Visual scanning - Number of commission errors | -0.70 Z-scores based on normative data. | Standard Deviation 0.28 |
| High Dose of Hydrocortisone | 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. | Alertness - Reaction time tonic alertness | -0.99 Z-scores based on normative data. | Standard Deviation 0.73 |
| High Dose of Hydrocortisone | 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. | Alertness - Reaction time phasic alertness | -1.10 Z-scores based on normative data. | Standard Deviation 0.66 |
| High Dose of Hydrocortisone | 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. | Semantic fluency | 0.09 Z-scores based on normative data. | Standard Deviation 1.18 |
| High Dose of Hydrocortisone | 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. | Phonemic fluency | 0.21 Z-scores based on normative data. | Standard Deviation 1.31 |
| High Dose of Hydrocortisone | 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. | Digit Span backwards-Working memory | -0.01 Z-scores based on normative data. | Standard Deviation 1.02 |
| High Dose of Hydrocortisone | 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. | Trail Making Test - Time condition A | -0.26 Z-scores based on normative data. | Standard Deviation 1.06 |
| High Dose of Hydrocortisone | 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. | Trail Making Test - Time condition B | 0.18 Z-scores based on normative data. | Standard Deviation 1.31 |
| High Dose of Hydrocortisone | 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. | Trail Making Test - Condition B/A | 0.36 Z-scores based on normative data. | Standard Deviation 1.48 |
Comparison: Rivermead Behavioural Memory Test (RBMT) - Immediate memoryp-value: 0.861Wilcoxon (Mann-Whitney)
Comparison: RBMT - Delayed memoryp-value: 0.668Wilcoxon (Mann-Whitney)
Comparison: RBMT-Delayed corrected for immediate memoryp-value: 0.713Wilcoxon (Mann-Whitney)
Comparison: 15 Words Test - Short-term memoryp-value: 0.028Wilcoxon (Mann-Whitney)
Comparison: 15 Words Test - Total immediate memoryp-value: 0.227Wilcoxon (Mann-Whitney)
Comparison: 15 Words Test - Learning Scorep-value: 0.13Wilcoxon (Mann-Whitney)
Comparison: 15 Words Test- Delayed memoryp-value: 0.106Wilcoxon (Mann-Whitney)
Comparison: 15 Words Test - Delayed corrected for total memoryp-value: 0.35Wilcoxon (Mann-Whitney)
Comparison: 15 Words Test - Recognitionp-value: 0.093Wilcoxon (Mann-Whitney)
Comparison: Digit Span forward - Short-term memoryp-value: 0.614Wilcoxon (Mann-Whitney)
Comparison: Rey Complex Figure - Immediate memoryp-value: 0.111Wilcoxon (Mann-Whitney)
Comparison: Rey Complex Figure - Delayed memoryp-value: 0.451Wilcoxon (Mann-Whitney)
Comparison: Divided attention-Reaction time auditory responsep-value: 0.905Wilcoxon (Mann-Whitney)
Comparison: Divided attention-Reaction time visual responsep-value: 0.502Wilcoxon (Mann-Whitney)
Comparison: Divided attention-Number of omission errorsp-value: 0.531Wilcoxon (Mann-Whitney)
Comparison: Divided attention-Number of commission errorsp-value: 0.681Wilcoxon (Mann-Whitney)
Comparison: Visual scanning - Reaction time for target stimulip-value: 0.713Wilcoxon (Mann-Whitney)
Comparison: Visual scanning - Number of omission errorsp-value: 0.229Wilcoxon (Mann-Whitney)
Comparison: Visual scanning - Number of commission errorsp-value: 0.329Wilcoxon (Mann-Whitney)
Comparison: Alertness - Reaction time tonic alertnessp-value: 0.192Wilcoxon (Mann-Whitney)
Comparison: Alertness - Reaction time phasic alertnessp-value: 0.164Wilcoxon (Mann-Whitney)
Comparison: Semantic fluencyp-value: 0.536Wilcoxon (Mann-Whitney)
Comparison: Phonemic fluencyp-value: 0.572Wilcoxon (Mann-Whitney)
Comparison: Digit span backward - Working memoryp-value: 0.632Wilcoxon (Mann-Whitney)
Comparison: Trail Making Test - Time condition Ap-value: 0.512Wilcoxon (Mann-Whitney)
Comparison: Trail Making Test - Time condition Bp-value: 0.861Wilcoxon (Mann-Whitney)
Comparison: Trail Making Test - Condition B/Ap-value: 0.958Wilcoxon (Mann-Whitney)
Comparison: Social cognitionp-value: 0.819Wilcoxon (Mann-Whitney)
Secondary
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.
Cardiovascular and metabolic risk factors, (pituitary) hormones and bone markers.
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).
Secondary
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.
The patients report common somatic complaints by filling in structured daily diaries.
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).
Secondary
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.
Quality of life questionnaires have to be filled in by the participant at his/her home place and have to be returned by post.
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).
Secondary
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.
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.
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).