Optimising Steroid Replacement in Patients With Adrenal Insufficiency

NCT03282487 | Unknown Phase 4

• 1 other identifier: 2016/09/05
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Adrenal insufficiency is a condition where the adrenal glands do not produce an adequate amount of steroid hormones. The aetiology of adrenal insufficiency can be primary or secondary. Patients will adrenal insufficiency have increased morbidity and mortality. In recent years there has been concern regarding what is the optimal dose and regimen of steroid replacement for patients. Unfortunately there is no accurate way of monitoring if a patient is on too much or too little steroid. We have shown in hypopituitary patients with secondary adrenal insufficiency that higher doses of hydrocortisone may be harmful. This reason for this is not fully understood. In recent years, a modified release hydrocortisone tablet (Plenadren) taken once per day (unlike conventional immediate release hydrocortisone which requires twice or thrice daily regimen) has come on the market. This tablet has shown to a have a steroid profile that more closely resembles normal physiology, avoiding the peak steroid levels that occur during thrice daily regimens, which may be of importance for improving outcome in adrenal insufficiency patients. It also shown improved cardiovascular risk factors, glucose metabolism and quality of life in compared to conventional treatment. The aim of our study is to assess the effect of hydrocortisone therapy on how the body uses and breaks down (metabolises) steroids. This will be done by several different research methods: by measuring markers of steroid action and metabolism in blood, urine and within the fat tissue under the skin in the abdomen. These results will be compared in the same patient while on their usual hydrocortisone and after switching to modified release hydrocortisone for 12 weeks, and to results from a normal healthy control group who are not on steroid replacement. This will be the first study to assess the impact of this new modified release hydrocortisone in relation to tissue steroid metabolism. The results will potentially help us to improve the treatment of patients with steroid deficiency and reduce the side effects seen in these patients.

Conditions

Adrenal Insufficiency

Keywords

cortisol; adrenal insufficiency; hypopituitarism; hydrocortisone

Outcome Measures

Primary Outcomes (3)

• Global corticosteroid metabolism

  Urinary steroid metabolite profiles.

  At baseline and after 12 weeks of Plenadren(intervention) treatment

• Adipose tissue corticosteroid metabolism

  Cortisol generation profile using adipose tissue microdialysis catheter

  At baseline and after 12 weeks of Plenadren(intervention) treatment

• Hepatic corticosteroid metabolism

  Serum Cortisol generation profile

  At baseline and after 12 weeks of Plenadren(intervention) treatment

Secondary Outcomes (2)

• Quality of Life questionnaires

  At baseline and after 12 weeks of Plenadren(intervention) treatment

• Potential biomarkers for adequacy of hydrocortisone replacement

  At baseline and after 12 weeks of Plenadren(intervention) treatment

Study Arms (3)

Conventional immediate release hydrocortisone

NO INTERVENTION

Modified release Hydrocortisone

ACTIVE COMPARATOR

12 weeks of modified release hydrocortisone (Plenadren)

Drug: Modified release hydrocortisone

Healthy control group

NO INTERVENTION

Same research laboratory measurements performed in a healthy control group for comparison to patient group

Interventions

Modified release hydrocortisone DRUG

Patients will switch from their usual conventional immediate release hydrocortisone to daily dose equivalent of modified release hydrocortisone (Plenadren®)

Also known as: Plenadren

Modified release Hydrocortisone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 18years of age with Primary Adrenal Insufficiency (Addison's disease) confirmed on biochemical testing.
• Male or female patients ≥ 18years of age with ACTH deficiency defined by a stimulated peak cortisol in response to insulin-induced hypoglycaemia or short synacthen testing \<400 nmol/l, with known organic pituitary disease, and no adjustment in hormone replacement for at least 3 months prior to study entry.
• Signed informed consent to participate in the study

You may not qualify if:

• Age \< 18 years
• Patients with acute medical or surgical illness
• Patients with advanced cardiac/pulmonary disease
• Patients with a terminal illness
• Patients on glucocorticoids for purposes other than ACTH deficiency
• Patients on agents that interfere with corticosteroid metabolism

Sponsors & Collaborators

• The Adelaide and Meath Hospital, incorporating The National Children's Hospital: lead

Study Sites (1)

Adelaide and Meath Hospital incorporating the National Childrens Hospital

Dublin, Ireland

Location

Related Publications (1)

• Dineen RA, Martin-Grace J, Ahmed KMS, Taylor AE, Shaheen F, Schiffer L, Gilligan LC, Lavery GG, Frizelle I, Gunness A, Garrahy A, Hannon AM, Methlie P, Eystein SH, Stewart PM, Tomlinson JW, Hawley JM, Keevil BG, O'Reilly MW, Smith D, McDermott J, Healy ML, Agha A, Pazderska A, Gibney J, Behan LA, Thompson CJ, Arlt W, Sherlock M. Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy. J Clin Endocrinol Metab. 2023 Nov 17;108(12):3178-3189. doi: 10.1210/clinem/dgad370.

  PMID: 37339332 DERIVED

MeSH Terms

Conditions

Adrenal Insufficiency; Hypopituitarism

Condition Hierarchy (Ancestors)

Adrenal Gland Diseases; Endocrine System Diseases; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Mark Sherlock

  Adelaide and Meath Hospital incorporating the national childrens hospital, Tallaght, Dublin, Ireland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Endocrinologist

Study Record Dates

• First Submitted: September 12, 2017
• First Posted: September 14, 2017
• Study Start: September 5, 2017
• Primary Completion: September 1, 2019
• Study Completion: December 1, 2019
• Last Updated: September 14, 2017

Record last verified: 2017-09

Locations

IE (1)