Objective Markers and New Indicators in AI Disease (OMNI-AID Study)

Study Overview
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Brief Summary
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This pilot study is designed to compare healthy volunteers with three groups of patients with adrenal insufficiency and a final group of patients receiving high dose steroids for anti-inflammatory purposes. The study will collect data on all 5 groups with the intention of identifying any novel markers or immunological indicators which may be used clinically to gauge the adequacy of steroid replacement treatment in patients with adrenal insufficiency.

Detailed Description
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Glucocorticoid replacement in adrenal insufficiency poses a significant challenge. If given too much, patients risk long term complications including diabetes, osteoporosis and cardiovascular disease. If, however they are given too little, patients can feel tired, unwell and may collapse as there is insufficient steroid hormone to cope with stress. Currently there is no single objective marker or outcome that can be measured to ascertain whether a patient is receiving optimum glucocorticoid replacement therapy. This study will investigate a selection of markers to examine whether they can be used to as indicators to gauge the adequacy of therapy. Finding an appropriate marker could unlock better care and outcomes for our patients with adrenal insufficiency .

Official Title
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Objective Markers and New Indicators in Adrenal Insufficiency Disease (OMNI-AID Study)

Conditions
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Adrenal Insufficiency

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 - 85 years Male or female Participants who are otherwise healthy enough to participate, as determined by pre-study medical history and physical examination Patient groups only: Diagnosed with AI for over 6 months according to standard diagnostic criteria or with a medical condition requiring acute high dose steroid therapy for anti-inflammatory purposes If diagnosed with AI, established on stable HC replacement or prednisolone replacement, dose not altered for at least 3 months Established on a stable dose of Fludrocortisone, if taking, dose not altered for at least 3 months Participants taking other hormone replacements (e.g. levothyroxine, testosterone or growth hormone in secondary adrenal insufficiency) are accepted providing that their replacement doses have not altered for at least 3 months Participants who are able and willing to give written informed consent to participate in the study. Exclusion Criteria: Participants with a diagnosis of Type 1 or Type 2 diabetes mellitus. Unable to give informed consent. Excessive caffeine intake above 500 mg per day. Taking supplements or herbal medications that the participant is unwilling or unable to stop prior to and during the study period e.g. St John's Wort (may decrease prednisolone levels), Cat's claw, Echinacea (immunomodulatory properties). Currently taking medications that alter CYP3A4 metabolism of glucocorticoids that the participant is unwilling or unable to stop prior to and during the study period e.g. phenytoin, phenobarbital, rifampicin, rifabutin, carbamazepine, primidone, aminogluethimide, itraconazole, ketoconazole, ciclosporin or ritonavir. Pregnancy, taking the oral contraceptive pill, or oral oestrogen replacement therapy due to the effects on cortisol binding globulin levels and determination of prednisolone levels. Transdermal oestrogen replacement is permitted. Females of child-bearing age will be asked to provide a urine sample for a pregnancy test at each visit. Diagnosis of growth hormone deficiency, untreated History of any medical, psychological or other condition, or use of any medications, including over-the-counter products, which, in the opinion of the investigators, would either interfere with the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy volunteers<br>Healthy volunteers whose data represents a negative control | |
| Prednisolone replacement group<br>Participants with adrenal insufficiency who are treated with replacement doses of prednisolone | |
| Hydrocortisone replacement group<br>Participants with adrenal insufficiency who are treated with replacement doses of hydrocortisone | |
| New adrenal insufficiency group<br>Participants who have recently been given a new diagnosis of adrenal insufficiency | |
| High dose steroids groups<br>Participants who are treated with high dose steroids for management of any medical condition to serve as a positive control | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Osteocalcin | Assesses bone health of each group by comparing total osteocalcin and undercarboxylated osterocalcin | Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| P1NP | Assesses bone health of each group by comparing P1NP | Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy. | 
| NTX | Assesses bone health of each group by comparing NTX | Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy. | 
| Heart Rate | recording observations- heart rate | Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy. | 
| Blood pressure | recording observations- blood pressure | Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy. | 
| Waist-Hip circumference | recording observations- Waist-Hip circumference ratios | Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy. | 
| Lipid profile (Total cholesterol, HDL, LDL and triglycerides) | measuring biochemical indicators of cardiovascular risk: total cholesterol, HDL, LDL and triglycerides | Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy. | 
| High sensitivity CRP | measuring biochemical indicators of cardiovascular risk: high sensitivity CRP | Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy. | 
| Glucose | measuring glucose | Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy. | 
| HbA1c | measuring HbA1c | Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy. | 
| Infection rates and severity | assessed by completion of the German National Cohort Questionnaire (GNCQ), questionnaires will cover socio-economic and socio-demographic factors, medical history, use of medications and health care, lifestyle factors, and questions related to environmental and occupational factors | Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy. | 
| Wellbeing | the short form health survey-36 (SF-36) | Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucocorticoids, Hydrocortisone, Prednisolone