Dissecting the Contribution of glucocorticoid metabolism in Mild Autonomous Cortisol Secretion: a randomised controlled trial of the 11β-HSD1 inhibitor SPI-62 (DC-MACS)

Research summary

We will conduct a randomised,double-blind,placebo controlled,Phase 2 study to evaluate the effect of the selective 11β-HSD1 inhibitor,SPI-62,6mg once daily for 12-weeks,on metabolic,bone and cognitive phenotype in patients with adrenal adenomas and evidence of MACS. 40 patients with MACS will be recruited from tertiary referral endocrine centres. All participants will have baseline investigations performed before treatment. We will collect clinical data by collecting biological samples including serum,urine,adipose tissue and microdialysis,as well as questionnaires and cognitive function tests. All participants will have baseline investigations performed during 3 visits in a pre-treatment period of up to 5 weeks duration. At visit 3 during the pre-treatment period,20 participants will be randomised to receive the active drug,SPI-62 (6mg) and 20 will receive placebo. Participants will be dispensed with one bottle of SPI-62 or placebo capsules in a double-blind manner,with sufficient supply for the first 4 weeks of administration,in accordance with their allocated treatment,and provided with dosing instructions. Participants will be instructed to commence taking the capsules the day after they receive the drugs at 09:00h (Day 1),and each day thereafter for 84 days (12 weeks). Additional bottles of SPI-62 or placebo capsules will be dispensed to each participant at their week 4 / Visit 4 and at week 8 / visit 5. The study will require 7 participant visits and 2 telephone calls over a total period of up to 20 weeks,including the pre treatment (3 visits),treatment (4 visits). Clinical data will be collected through the acquisition of biological samples (serum,urine,saliva,adipose tissue and microdialysis),as well as monitoring of clinical parameters such as blood pressure and glucose levels,questionnaires,cognitive function tests,imaging,and routine safety monitoring. The primary and secondary endpoints of the study will be assessed after 11-12 weeks of treatment,apart from salivary cortisol and cortisone,urine steroids lipids and bone markers,which will additionally be assessed after 4 and 8 weeks of treatment. Continuous glucose monitoring will only be assessed after 4 weeks. After 12 weeks of treatment,all study treatments will be stopped,and a follow-up phone call will occur 4 weeks later to determine if there are any delayed adverse effects with the option to schedule an in person visit if deemed necessary by the investigative team. This study will determine whether SPI-62 can improve the adverse metabolic,bone,and cognitive phenotype associated with MACS. The study will be conducted with the support of the Diabetes Trials Unit (DTU) within OCDEM. DTU will provide project management support,statistical support and generate the trial database and report forms

Principal Investigator

Prof Jeremy Tomlinson

Contact us

Email: diabetes.research1@ouh.nhs.uk

IRAS number

1004412