Effects and Interactions of Liquorice and Grapefruit on Glucocorticoid Replacement Therapy in Addison's Disease

NCT01271296 | Completed

• 4 other identifiers: 3.2007.2620 (REK)17775 (NSD)07/5829 (SHdir)3.2007.2620
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Addison's disease is a rare disease, wherein the adrenals can not produce sufficient steroid hormones (cortisol and aldosterone). Patients with Addison's disease report impaired subjective health status, and they have increased all-cause mortality. Conventional therapy is by oral replacement of glucocorticoid and mineralocorticoid hormones, but this strategy imperfectly mimic the diurnal cortisol variations, and render the patients both over- and under-treated. Anecdotally, some patients with adrenal insufficiency may benefit from the use of various nutritional compounds. We hypothesised that liquorice and grapefruit altered the metabolism and absorption of cortisone acetate.

Conditions

Addison Disease

Keywords

Addison Disease; Pharmacokinetics; Hormone Replacement Therapy; cortisone acetate; Quality of Life

Outcome Measures

Primary Outcomes (1)

• AUC Serum Cortisol - Levels of cortisol in serum during the first 2.6 hours after oral administration of cortisone acetate.

  The area under the curve (AUC) of cortisol is calculated based on serum time-series sampling (every 20 minutes for 2.6 h after oral administration of cortisone acetate). The AUCs obtained during liquorice and grapefruit juice intakes are compared to the baseline assessment (without these nutritional compounds). All other pharmacokinetic properties (primary and secondary outcome measures) are compared analogously.

  Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.

Secondary Outcomes (19)

• Serum Cortisol levels at the end of time-series sampling (t=160min)

  Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.

• Serum Cortisone levels at the end of time-series sampling (t=160min)

  Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.

• Saliva Cortisol levels at the end of time-series sampling (t=160min)

  Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.

• Saliva Cortisone levels at the end of time-series sampling (t=160min)

  Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.

• Time of maximum concentration of serum Cortisol

  Outcome measures are assessed when all subjects have completed the study, approximately 1.5-2.0 years after study start.

Study Arms (3)

Liquorice

ACTIVE COMPARATOR

Liquorice eq to 150 mg glycyrrhizinic acid. Results are compared to a baseline assessment without liquorice/grapefruit juice ingestion.

Dietary Supplement: Liquorice

Grapefruit juice

ACTIVE COMPARATOR

200 ml pink grapefruit juice three times a day. Results are compared to a baseline assessment without liquorice/grapefruit juice ingestion.

Dietary Supplement: Grapefruit Juice

Baseline

NO INTERVENTION

Baseline assessment without intake of liquorice or grapefruit juice

Interventions

Liquorice DIETARY_SUPPLEMENT

24 gram liquorice eq. to 150 mg glycyrrhizinic acid, taken orally, for three days.

Liquorice

Grapefruit Juice DIETARY_SUPPLEMENT

200 ml pink grapefruit juice three times a day, taken orally, for three days.

Grapefruit juice

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Verified diagnosis of adrenal insufficiency (Addison's disease)
• Stable cortisone acetate replacement therapy
• Written informed consent

You may not qualify if:

• Malignant disease
• Pharmacological treatment with other glucocorticoids
• Pregnancy
• Current minor disease (ie the flu)
• Major disease or accident requiring hospitalization the last three months
• Use of grapefruit juice or liquorice the last two weeks before study start
• Blood pressure above 150mmHg systolic or 90 mmHg diastolic.

Sponsors & Collaborators

• Haukeland University Hospital: lead

Study Sites (1)

Haukeland University Hospital, Helse-Bergen HF

Bergen, 5020, Norway

Location

MeSH Terms

Conditions

Addison Disease

Interventions

Glycyrrhiza glabra extract

Condition Hierarchy (Ancestors)

Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Paal Methlie, MD

  University of Bergen. Helse-Bergen HF

  PRINCIPAL INVESTIGATOR

• Kristian Løvås, MD, PhD

  University of Bergen. Helse-Bergen HF.

  PRINCIPAL INVESTIGATOR

• Eystein S Husebye, Prof, MD

  University of Bergen. Helse-Bergen HF.

  PRINCIPAL INVESTIGATOR

• Ernst A Lien, Prof. MD.

  University of Bergen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 22, 2010
• First Posted: January 6, 2011
• Study Start: April 1, 2008
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: January 17, 2011

Record last verified: 2010-12

Locations

NO (1)