Clinical trial NCT02934399: Dynamic Hormone Diagnostics in Endocrine Disease
Official title: Dynamic Hormone Diagnostics (Ultradian)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Adrenal Insufficiency
Congenital Adrenal Hyperplasia
Cushing Syndrome
Growth Hormone Deficiency
Acromegaly
Primary Hyperaldosteronism
Keywords: dynamic hormone diagnostics
adrenal insufficiency
congenital adrenal hyperplasia
primary hyperaldosteronism
cushing syndrome
growth hormone deficiency
acromegaly
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
Collaborators: name: Karolinska Institutet
name: University Hospitals Bristol and Weston NHS Foundation Trust
name: Evaggelismos Hospital, Greece
First posted: 2016-10-17
Enrollment: 528
Sex: ALL
Minimum age (years): 18
Maximum age (years): 68
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Healthy Controls and patients with established Cushing syndrome, Adrenal Insufficiency, Congenital adrenal hyperplasia, Primary hyperaldosteronism, Acromegaly and Growth hormone deficiency

Brief summary: The study will investigate 27 hour profiles of hormones in the subcutaneous tissue of healthy subjects and patients with Addison's, Congenital Adrenal Hyperplasia, Growth Hormone Deficiency, acromegaly, Cushings and Primary Hyperaldosteronism during conventional diagnostic and therapeutic follow-up.

The 27 hour monitoring by ULTRADIAN takes into account the rhythm of hormones throughout the day. It is hoped that this information may in the future improve and simplify diagnostic procedures. Follow-up of patients in endocrinology still remains difficult including clinical signs of over and under-treatment, questionnaires of quality of life and blood testing necessitating often retesting. Simplification of the diagnostic procedure by obtaining detailed knowledge about the rhythm of hormones may contribute to the improvement and individualization of treatment and may decrease morbidity and mortality of endocrine patients.

Detailed description: Microdialysis fluid will be collected from all participants using the ULTRADIAN dynamic diagnostics system. This is a 3-component collection system which can easily be attached to a belt and allows participants to continue with their normal everyday activities whilst undergoing sampling. The micro-fractions are minute, the volume would normally be by far too small to use with current immunoassays.

ULTRADIAN will overcome this hurdle by introducing two novel techniques; ultrasensitive liquid chromatography tandem mass spectroscopy (LCMS/MS) for steroid hormones, and the proximity extension assay (PEA®), which allows the simultaneous assay of up to 96 analytes in only 1 µL fluid.

The microdialysis sampling will be performed in addition to the conventional diagnostic sampling, and during normal follow-up of patients.

Eligibility criteria: Inclusion Criteria:

* Healthy male and female subjects aged 18-68 years, non-smokers or regular smokers of greater than 6 cigarettes a day, BMI 16-29
* Male and female Cushing's syndrome aged 18-68 years with biochemically confirmed based on cortisol and ACTH measurements, dexamethasone suppression test and 1 of the following positive investigations (24 hour urine cortisol, salivary/serum cortisol profile). Visible tumour in the pituitary and/or one of the following positive tests pointing to pituitary source for ACTH overproduction (bilateral petrosal sinus sampling, corticotropin releasing hormone test, high dose dexamethasone suppression test) or adrenal tumour considered fit for surgery. No contraceptives for 6 weeks prior to sampling (females only). Patients on medical therapy e.g. metyrapone for Cushings to have a 2 week washout off treatment prior to sampling
* Male and female aged 18 -68 years with biochemically confirmed adrenal insufficiency based on basal cortisol and ACTH measurements and/or Synacthen test +/- adrenal antibodies, and on oral hydrocortisone or cortisone acetate glucocorticoid replacement therapy
* Female aged 18-68 years with biochemically confirmed salt-wasting or simple virilising CAH based on 17OHP, cortisol, androgen, renin and ACTH measurements; disease causing mutation in CYP21A2 and/or synacthen testing.
* Male and female subjects aged 18 -68 years with biochemical confirmation of PHA based on a valid pathological aldosterone/renin ratio and non-suppressible aldosterone levels on one of the currently used confirmatory tests (saline/oral fludrocortisone test). Unilateral only - diagnostic CT and/or adrenal vein sampling
* Male and female subjects aged 18-68 years with biochemically confirmed GHD (arginine growth hormone releasing hormone test, insulin tolerance test, known pituitary disease with confirmed pan hypopituitarism)
* Male and female aged 18-68 years with biochemically confirmed acromegaly (oral glucose tolerance test or GH day curve and diagnostic insulin growth factor 1 levels) with radiological evidence of a pituitary adenoma.

Exclusion Criteria:

* Healthy controls undergoing or planning pregnancy or lactating women. Presence of any unstable pathological condition in past 3 months. On any regular prescribed medications (except contraception). Prior or current history of an endocrine disorder. Known allergy to Lignocaine, plasters. Current or past steroid therapies (oral, inhaled, parenteral or topical) or other interfering medication in last 3 months. Regular alcohol intake great then 26units of alcohol per week.Taking of any investigational drug within the past two months. Abuse of illicit drugs. Occasional smokers of cigarettes not able to abstain for sampling period or smoking less than 6 cigarettes a day. Needle phobia. Interfering diet/over the counter herbal remedies in last 14 days.
* Cushing syndrome: Undergoing or planning pregnancy (females only). Known allergy to Lignocaine. Adrenal cancer (post-operative histology diagnosis),cyclic Cushings, squamous cell lung carcinoma, bronchial carcinoid and occult ectopic Cushings. Concurrent use of steroid therapy for any other medical condition (oral, inhaled, parenteral or topical)
* Adrenal insufficiency: Undergoing or planning pregnancy, known allergy to Lignocaine, use of other steroid medications other than their standard glucocorticoid and fludrocortisone replacement, other interfering medication or diet within 2 weeks of sampling.
* CAH: Males, females undergoing or planning pregnancy, known allergy to Lignocaine, use of other steroid medications other than their standard glucocorticoid and fludrocortisone replacement or other interfering medication or diet within 2 weeks of sampling
* Primary hyperaldosteronism: Undergoing or planning pregnancy (females only), known allergy to Lidocaine, known adrenal failure and/or on steroid therapy (oral, inhaled, parenteral or topical), concurrent use of interfering medication ( i.e. specific interfering antihypertensive medication) or diet within 2-4 weeks of ultradian sampling
* GHD: Undergoing or planning pregnancy (females only) or known allergy to Lignocaine
* Acromegaly: Undergoing or planning pregnancy (females only), known allergy to Lignocaine treatment with somatostatin analogues and other interfering medication (e.g. oestrogens)

Primary outcomes:
measure: steroids
timeFrame: 27 hours
measure: androgens
timeFrame: 27 hours
measure: mineralocorticoids
timeFrame: 27 hours
measure: ACTH
timeFrame: 27 hours
measure: growth hormone
timeFrame: 27 hours
measure: steroids in Addison disease
timeFrame: 27 hours
measure: steroids in congenital adrenal hyperplasia
timeFrame: 27 hours
measure: androgen in congenital adrenal hyperplasia
timeFrame: 27 hours
measure: growth hormone in acromegaly
timeFrame: 27 hours
measure: growth hormone in growth hormone deficiency
timeFrame: 27 hours
measure: mineralocorticoids in primary hyperaldosteronism
timeFrame: 27 hours
Secondary outcomes:
measure: Intra-individual variability and the accuracy of steroids hormones
timeFrame: 27 hours
measure: Intra-individual variability and the accuracy of androgens
timeFrame: 27 hours
measure: Intra-individual variability and the accuracy of mineralocorticoids
timeFrame: 27 hours
measure: Intra-individual variability and the accuracy of growth hormone
timeFrame: 27 hours
measure: Intra-individual variability and the accuracy of ACTH
timeFrame: 27 hours
Other outcomes:
Locations:
city: Athen
country: Greece
facility: Evangelissmos hospital
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Stockholm
country: Sweden
facility: Karolinska Institutet
city: Bristol
country: United Kingdom
facility: Bristol University hospital
Study officials:
affiliation: University of Bristol
name: Stafford Lightman, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Sophie Bensing, MD phD
role: PRINCIPAL_INVESTIGATOR
affiliation: Evaggelismos Hospital
name: Stylianos Tsagarakis, Professor
role: PRINCIPAL_INVESTIGATOR
References: