Mild autonomous cortisol secretion due to an adrenal adenoma Nutritional, Metabolic, Endocrine
Conditions
Interventions
40 patients with Mild Autonomous Cortisol Secretion (MACS) will be recruited and undergo 2 days of baseline investigations. They will then be randomized using an online tool to receive the IMP (SPI-62
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant is willing and able to give informed consent for participation in the trial 2. Aged 18 years or above 3. 09.00 h serum cortisol >51 nmol/L after overnight dexamethasone (1 mg) within the last 6 months performed in the absence (for at least 4 weeks prior to testing) of concomitant estrogen-containing medication. 4. Adrenal adenoma(s) that has (have) not been surgically removed, and with benign characteristics on cross-sectional imaging. 5. Body mass index 18 to 45 kg/m2 6. Stable dose of current regular antihypertensive and/or glucose-lowering medication for at least 12 weeks prior to trial entry. 7. Female participants of childbearing potential and male participants whose partner is of childbearing potential must be willing to ensure that they and their partner use effective contraception during the trial and for 90 days thereafter. 8. In the Investigator’s opinion, the participant is able and willing to comply with all trial requirements. 9. Participant is willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the trial
Exclusion criteria
Exclusion criteria: 1. Female participant is pregnant, lactating, or planning pregnancy during the course of the trial 2. Scheduled elective surgery or other procedures requiring general anaesthesia are required during the course of the trial 3. Participants with a life expectancy of less than 6 months 4. A diagnosis of idiopathic thrombocytopenic purpura or any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial 5. A clinical phenotype consistent with classical Cushing’s syndrome (e.g. thin skin, easy bruising, proximal myopathy) 6. Evidence from medical records of elevated aldosterone/renin ratio (above local reference range) on blood sampling 7. Renal impairment indicated by eGFR 500 ms, uncorrected QT interval >600 ms, or evidence of significant, life-threatening arrhythmia or bradycardia (heart rate 35 units per week female and >50 units per week male, or other indicators of possible alcohol misuse) in the opinion of the Investigator 15. Uncontrolled hypertension (>160/100 mmHg) 16. Type 1 diabetes or Type 2 diabetes requiring medication (with the exception of metformin monotherapy) 17. Recent (within the last 3 months) or planned night-shift work during the duration of the study 18. Contraindication to any of the study treatments or known or suspected hypersensitivity ?to the investigational product, compounds of the same class, other study treatments or any excipients 19. Participation in an interventional study in which involvement was completed less than 12 weeks before recruitment into the current study 20. Administration of any vaccine within 4 weeks prior to randomization or planned during the trial 21. SARS-CoV-2 infection within 4 weeks, or hospitalization for COVID-19 disease within 6 months, prior to randomization 22. Any major surgery within 1 month prior to randomization or planned during the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Glucose disposal as measured across the hyperinsulinaemic euglycaemic clamp using stable isotope glucose tracers at baseline and 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Serum markers of bone turnover including Procollagen type 1 N-terminal pro-peptide, type I collagen cross-linked N-telopeptide and osteocalcin measured using ELISAs at 4, 8 and 11 weeks 2. Cognitive function assessed using the CogState battery of tests at baseline and 11 weeks 3. 24-hour ambulatory blood pressure measurements using an ambulatory blood pressure monitor at baseline and 11 weeks 4. Endogenous glucose production rate during a hyperinsulinaemic euglycaemic clamp measured using stable isotope glucose tracers at baseline and 11 weeks 5. Total and regional lean and fat mass on DXA scan and intra-abdominal fat mass on single slice CT image at baseline and 11 weeks 6. Steroid metabolites measured by gas chromatography, mass spectrometry in a timed overnight urine sample at 4, 8 and 11 weeks 7. Circulating inflammatory cytokines, isolation of peripheral blood mononuclear cells and defining their response to inflammatory stress measured using cell proliferation assays and ELISAs at baseline and 11 weeks 8. Continuous glucose monitoring using interstitial glucose sensors at baseline, 4-6 and 8-10 weeks 9. Gene expression changes measured in adipose tissue biopsies using PCR gene expression analysis at baseline and 11 weeks 10. Safety and tolerability measured using clinical data and serum biochemical assessments at baseline and 11 weeks | — |
Countries
United Kingdom
Outcome results
None listed