Dynamic Hormone Diagnostics in Endocrine Disease

Acromegaly Clinical Trial

— ultradian  

Official title:

Dynamic Hormone Diagnostics (Ultradian)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02934399
• Other study ID #: REKno 2015/872
• Status: Completed
• Start date: October 2016
• Est. completion date: November 14, 2023

Study information

• Verified date: August 2020
• Source: Haukeland University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 528
• Est. completion date: November 14, 2023
• Est. primary completion date: November 14, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 68 Years

Eligibility

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)

Related Conditions & MeSH terms

• Acromegaly
• Adrenal Hyperplasia, Congenital
• Adrenal Insufficiency
• Adrenogenital Syndrome
• Congenital Adrenal Hyperplasia
• Cushing Syndrome
• Growth Hormone Deficiency
• Hyperaldosteronism
• Hyperplasia
• Primary Hyperaldosteronism

Intervention

Other:
• 27 hour subcutaneous fluid sampling
One hour prior to the microdialysis catheter insertion the participants will be asked to receive a local anaesthetic on the injection site for the microdialysis catheter. Lignocaine 1% will be injected subcutaneously at a localised site on the abdomen covering a horizontal area of about 5cm after a brief acclimatisation period at the hospital. A sterile linear catheter will be inserted using aseptic precautions at the anaesthetised site on the abdomen. The catheter is connected at one end to the microdialysis pump, and at the other end to the automated collection device. Subcutaneous tissue microdialysis samples will be collected regularly for the duration of the sampling period (27 hours).

Locations

Country	Name	City	State
Greece	Evangelissmos hospital	Athen
Norway	Haukeland University Hospital	Bergen
Sweden	Karolinska Institutet	Stockholm
United Kingdom	Bristol University hospital	Bristol

Sponsors (4)

Lead Sponsor	Collaborator
Haukeland University Hospital	Evaggelismos Hospital, Greece, Karolinska Institutet, University Hospitals Bristol and Weston NHS Foundation Trust

Countries where clinical trial is conducted

Greece,  Norway,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	steroids	Physiological hormonal curve by sampling of 27h subcutaneous fluid to measure steroids	27 hours
Primary	androgens	Physiological hormonal by sampling of 27h subcutaneous fluid to measure androgens	27 hours
Primary	mineralocorticoids	Physiological hormonal curve by sampling of 27h subcutaneous fluid to measure mineralocorticoids	27 hours
Primary	ACTH	Physiological hormonal curve by sampling of 27h subcutaneous fluid to measure ACTH	27 hours
Primary	growth hormone	Physiological hormonal curve by sampling of 27h subcutaneous fluid to measure growth hormone	27 hours
Primary	steroids in Addison disease	Hormonal curve by sampling of 27h subcutaneous fluid to measure steroids	27 hours
Primary	steroids in congenital adrenal hyperplasia	Hormonal curve by sampling of 27h subcutaneous fluid to measure steroids	27 hours
Primary	androgen in congenital adrenal hyperplasia	Hormonal curve by sampling of 27h subcutaneous fluid to measure androgens	27 hours
Primary	growth hormone in acromegaly	Hormonal curve by sampling of 27h subcutaneous fluid to measure growth hormone	27 hours
Primary	growth hormone in growth hormone deficiency	Hormonal curve by sampling of 27h subcutaneous fluid to measure growth hormone	27 hours
Primary	mineralocorticoids in primary hyperaldosteronism	Hormonal curve by sampling of 27h subcutaneous fluid to measure mineralocorticoids	27 hours
Secondary	Intra-individual variability and the accuracy of steroids hormones	comparison of steroids levels in repetitive testing	27 hours
Secondary	Intra-individual variability and the accuracy of androgens	comparison of androgens levels in repetitive testing	27 hours
Secondary	Intra-individual variability and the accuracy of mineralocorticoids	comparison of mineralocorticoids levels in retesting by microdialysis	27 hours
Secondary	Intra-individual variability and the accuracy of growth hormone	comparison of growth hormone levels in retesting by microdialysis	27 hours
Secondary	Intra-individual variability and the accuracy of ACTH	comparison of ACTH levels in retesting by microdialysis	27 hours