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

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

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.

Study Overview

• Status: Unknown
• Conditions: Adrenal Insufficiency

Detailed Description

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 .

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Sirazum Choudhury, MBBS MRCP; Phone Number: 07555717544; Email: steroids@imperial.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, W12 8RF
    • Recruiting
    • Imperial College Healthcare NHS Trust
    • Contact: Sirazum Choudhury, MBBS BSc; Phone Number: 07555717544; Email: steroids@imperial.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Individuals with either primary or secondary adrenal insufficiency who are currently receiving glucocorticoid replacement therapy with hydrocortisone or prednisolone.

Healthy volunteers will serve as positive controls.

Patients on high (anti-inflammatory) doses of steroids for any other medical condition will serve as positive controls.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
Healthy volunteers; Healthy volunteers whose data represents a negative control
Prednisolone replacement group; Participants with adrenal insufficiency who are treated with replacement doses of prednisolone
Hydrocortisone replacement group; Participants with adrenal insufficiency who are treated with replacement doses of hydrocortisone
New adrenal insufficiency group; Participants who have recently been given a new diagnosis of adrenal insufficiency
High dose steroids groups; 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?

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.

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: National Institute for Health Research, United Kingdom

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Anticipated): April 2, 2021
• Study Completion (Anticipated): April 2, 2021

Study Registration Dates

• First Submitted: July 31, 2018
• First Submitted That Met QC Criteria: July 31, 2018
• First Posted (Actual): August 6, 2018

Study Record Updates

• Last Update Posted (Actual): August 15, 2019
• Last Update Submitted That Met QC Criteria: August 13, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Prednisolone; Glucocorticoids; Hydrocortisone
• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenal Gland Diseases; Adrenal Insufficiency
• Other Study ID Numbers: 18HH4425; 216757 (Other Identifier: IRAS ID); 18/LO/0069 (Other Identifier: REC reference number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There are currently no plans to share individual data with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No