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

NCT ID: NCT01271296

Last Updated: 2011-01-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2009-01-31

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.

Detailed Description

In the present study, cortisone acetate absorption and metabolism are assessed in subjects with Addison's disease on three occasions. On the first occasion, the subjects are on their regular diet, but avoid ingestion of grapefruit and liquorice. At the end of the baseline assessment the order of the nutritional compounds (liquorice-grapefruit juice or grapefruit juice-liquorice) to be investigated in the next two assessments are randomised.

On the two next occasions, the absorption and metabolism of cortisone acetate is studied when study subjects consume liquorice and grapefruit juice. Between the use of grapefruit and liquorice there is a wash out period of at least 3 weeks.

For studies on liquorice effects, the subjects ingest 24-gram liquorice per day (equivalent of 150-mg glycyrrhizinic acid per day). For studies on grapefruit juice effects, subjects drink 200-ml grapefruit juice three times a day for three days. They maintain their regular medication and usual diet.

Time-series of cortisol and cortisone are obtained in serum and saliva samples on the third day of liquorice/grapefruit juice use. 24-hour urine is also collected.

Measurements of cortisol and metabolites in serum and saliva are used to calculate pharmacokinetical parameters. The measurements from samples obtained when using the investigated nutritional compounds are compared to the baseline assessment in each subject. Metabolites in 24-hour urine are compared similarly to investigate changes in urinary excretion, and to estimate the activity of enzymes involved in the metabolism of cortisol (5alfa-reductase, 5beta-reductase, cytochrome P450 3A4 system, 11-beta hydroxysteroid dehydrogenase).

Conditions

Addison Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Liquorice

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

Group Type: ACTIVE_COMPARATOR

Liquorice

Intervention Type: DIETARY_SUPPLEMENT

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

Grapefruit juice

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

Group Type: ACTIVE_COMPARATOR

Grapefruit Juice

Intervention Type: DIETARY_SUPPLEMENT

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

Baseline

Baseline assessment without intake of liquorice or grapefruit juice

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Liquorice

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

Intervention Type: DIETARY_SUPPLEMENT

Grapefruit Juice

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

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Haukeland University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Helse-Bergen HF, Haukeland University Hospital

Principal Investigators

Paal Methlie, MD

Role: PRINCIPAL_INVESTIGATOR

University of Bergen. Helse-Bergen HF

Kristian Løvås, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Bergen. Helse-Bergen HF.

Eystein S Husebye, Prof, MD

Role: PRINCIPAL_INVESTIGATOR

University of Bergen. Helse-Bergen HF.

Ernst A Lien, Prof. MD.

Role: PRINCIPAL_INVESTIGATOR

University of Bergen

Locations

Haukeland University Hospital, Helse-Bergen HF

Bergen, , Norway

Countries

Norway

Other Identifiers

17775 (NSD)

Identifier Type: OTHER

Identifier Source: secondary_id

07/5829 (SHdir)

Identifier Type: OTHER

Identifier Source: secondary_id

3.2007.2620

Identifier Type: OTHER

Identifier Source: secondary_id

3.2007.2620 (REK)

Identifier Type: -

Identifier Source: org_study_id