The primary aim of this study is to investigate the recovery of the circadian rhythm of the hypothalamic-pituitary-adrenal axis during a glucocorticoid tapering regime. Secondary objectives include the effect of a tapering regime on melatonin rhythm…
ID
Source
Brief title
CURVE
Condition
- Adrenal gland disorders
- Autoimmune disorders
- Vascular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study endpoint is change in peak cortisol levels at acrophase during a
glucocorticoid tapering regime.
Secondary outcome
Secondary endpoints include the effect on cortisol ratios or indices of
cortisol production, which might prove to be helpful in assessing adrenal
function or might be suggestive for impaired recovery or adrenal insufficiency.
Furthermore, the effect of the tapering regime on melatonin rhythm, cytokine
profile, complaints compatible with secondary glucocorticoid-induced adrenal
insufficiency, quality of life, fatigue and sleep quality.
Background summary
Glucocorticoids are extensively used for a wide-variety of diseases. In many
diseases, amongst others rheumatic diseases, high-dose glucocorticoids are
administered to control disease activity. These supra-physiological
glucocorticoid doses suppress the endogenous cortisol production and disrupt
the circadian rhythm of the hypothalamic-pituitary-adrenal (HPA) axis. In order
to prevent relapses and to give the adrenal glands time to recover the
endogenous cortisol production, tapering regimes are used for glucocorticoid
withdrawal. However, no longitudinal studies have investigated the effect of a
tapering regime on the recovery of the circadian rhythm of the HPA axis and the
relation with complaints possibly compatible with secondary adrenal
insufficiency.
Study objective
The primary aim of this study is to investigate the recovery of the circadian
rhythm of the hypothalamic-pituitary-adrenal axis during a glucocorticoid
tapering regime. Secondary objectives include the effect of a tapering regime
on melatonin rhythm, cytokine profile, complaints compatible with secondary
glucocorticoid-induced adrenal insufficiency and quality of life, fatigue and
sleep quality.
Study design
This is a longitudinal observational pilot study.
Study burden and risks
Burden: On seven separate days in an 8-month period subjects will collect
saliva approximately every one or two hour during a 24-hour period. The 24-hour
sampling will take place at prednisolone dosages of 10 mg, 7,5 mg, 5 mg, 2,5 mg
and 4 weeks, 3 months and 6 months after discontinuation of the prednisolone.
In addition, subjects will collect 24-hour urine during the seven 24-hour time
points. Blood samples will be drawn at the following visits to the outpatient
clinic at 7 time points. Questionnaires regarding somatic complaints, quality
of life, fatigue, anxiety and depression and sleep will be completed at the
outpatient clinic at 7 time points. At the last visit a Synacthen test will be
performed to test the adrenal function.
The healthy controls will only collect saliva and urine during an 24 hour
period. They will not undergo any of the other measurements.
Risk: In this observational study, a glucocorticoid tapering regime according
to standard patient care in the University Medical Center Groningen (UMCG) will
be used. Saliva and urine collection are safe and not invasive. At 7 time
points blood samples will be drawn. Blood sampling will be performed
simultaneously with blood sampling for standard patient care at five of the 7
time points. The Synacthen test is the standard diagnostic test to diagnose
adrenal insufficiency. The adrenal glands will be stimulated with synthetic
ACTH (Synacthen) to study the capacity of the glands to produce a maximum level
of cortisol. Side effects are transient and rarely severe.
Group relatedness: In subjects with GPA and MPA the glucocorticoid tapering
regime is a uniform protocol, which is used in several hospitals.
Benefit: this study will give insight in the recovery of the HPA axis and
whether recovery or impaired recovery might be related to commonly expressed
complaints by patients while on a tapering regime. Therefore this study will
add important information and might serve as pilot for future studies comparing
different tapering regimes which should ultimately minimize complaints of
patients and the risks of secondary glucocorticoid-induced adrenal
insufficiency.
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
Patient with newly diagnosed granulomatosis with polyangiitis or microscopic polyangiitis who received standard glucocorticoid induction protocol
Patients with a relapse of granulomatosis with polyangiitis or microscopic polyangiitis who received standard glucocorticoid induction protocol
Provide written informed consent
Exclusion criteria
Applicable for patients and healthy controls
Age < 18 years
Use of > 7,5 mg of glucocorticoids for more than 4 consecutive weeks within 6 months prior to study inclusion.
Premenopausal women (because of effects of estrogens on cortisol binding globulin and because of differences in HPA axis functioning in the luteal or follicular phase)
Postmenopausal women using oral contraceptives or estrogen replacement therapy (since estrogens increase the hepatic production of cortisol binding globulin)
A history of endogenous hypocortisolism or hypercortisolism prior to this study
Work in shifts or have a documented severely disturbed sleep pattern
Not able to perform saliva sampling
Persons who have a significant other medical condition (e.g. hepatic, respiratory, cardiovascular or gastrointestinal) which, in the opinion of the investigator, may interfere with the interpretation of results or efficacy evaluations
Traveled through time zones with more than two hours time difference within the last month prior to this study
Use of exogenous melatonin within the last 6 months prior to this study
A documented depression
Subjects who are in a stressful situation (for example, death of a relative), which in the opinion of the investigator, may interfere with the interpretation of results or efficacy evaluations
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL49307.042.14 |
| OMON | NL-OMON29371 |