Clinical trial NCT03615859: Objective Markers and New Indicators in AI Disease (OMNI-AID Study)
Official title: Objective Markers and New Indicators in Adrenal Insufficiency Disease (OMNI-AID Study)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Adrenal Insufficiency
Keywords: Glucocorticoids
Hydrocortisone
Prednisolone
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2018-08-06
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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.

Brief summary: 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: 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 .

Eligibility criteria: 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.

Primary outcomes:
measure: Osteocalcin
timeFrame: Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy.
Secondary outcomes:
measure: P1NP
timeFrame: Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy.
measure: NTX
timeFrame: Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy.
measure: Heart Rate
timeFrame: Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy.
measure: Blood pressure
timeFrame: Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy.
measure: Waist-Hip circumference
timeFrame: Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy.
measure: Lipid profile (Total cholesterol, HDL, LDL and triglycerides)
timeFrame: Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy.
measure: High sensitivity CRP
timeFrame: Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy.
measure: Glucose
timeFrame: Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy.
measure: HbA1c
timeFrame: Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy.
measure: Infection rates and severity
timeFrame: Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy.
measure: Wellbeing
timeFrame: Single time point for controls. Steroid replacement patients will have been on at least 4 months of stable therapy.
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Imperial College London
name: Karim Meeran, MBBS BSc MD
role: PRINCIPAL_INVESTIGATOR
References: