Acute Consequences Of Food-induced Glucocorticoid Secretion In Healthy Individuals

NCT05167084 | Completed Early Phase 1

• 1 other identifier: EKNZ 2021-01507
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

In a randomized, cross-over study, 20 healthy volunteers will receive a block and replace therapy that mimics physiological GC rhythm (metyrapone plus hydrocortisone) or placebo. Participants will undergo two identical overfeeding periods with each treatment. With the block and replace therapy, food-induced GC peak will be suppressed. Metabolic and autonomic parameters will be compared to reveal, whether GCs mediate the physiological adaptions to excessive food intake. Understanding acute effects of GCs upon food intake is critical, since repetitive disruptions of GC secretion may become harmful in chronic conditions.

Conditions

Glucocorticoid Effect

Keywords

cortisol; overfeeding; glucocorticoids; insulin sensitivity

Outcome Measures

Primary Outcomes (1)

• Insulin sensitivity

  Change in insulin sensitivity assessed with a mixed meal tolerance test

  Two 8-day intervention periods

Secondary Outcomes (27)

• Cortisol (nmol/l) total and free

  Two 8-day intervention periods

• Renin

  Two 8-day intervention periods

• Aldosterone (Adrenal Steroid Hormones)

  Two 8-day intervention periods

• Pregnenolon (Adrenal Steroid Hormones)

  Two 8-day intervention periods

• Progesteron (Adrenal Steroid Hormones)

  Two 8-day intervention periods

Other Outcomes (5)

• IL-6 (Inflammatory markers)

  Two 8-day intervention periods

• IL-1RA (Inflammatory markers)

  Two 8-day intervention periods

• IL-8 (Inflammatory markers)

  Two 8-day intervention periods

Study Arms (2)

Metyrapone And Hydrocortisone

EXPERIMENTAL

During one of the study periods, subjects receive hydrocortisone 19.9 mg/d subcutaneously via a pump in a pulsed fashion (eight times/day) and metyrapone per os (starting with a dose of 500 mg/d, then the dose will be increased the next days until 2500mg/d is achieved).

Drug: Metyrapone 250 mg Oral Tablets; Drug: Hydrocortisone 19,9mg s.c., pulsatile with a flow rate of 10μl/s

Placebo

PLACEBO COMPARATOR

During the other study period, subjects receive placebo (0,9% NaCl solution) 19.9 mg/d subcutaneously via a pump in a pulsed fashion and the same dose of placebo tablets p.o instead of metyrapone.

Drug: Placebo 250 mg Tablets; Drug: Placebo (0,9% NaCl solution)

Interventions

Metyrapone 250 mg Oral Tablets DRUG

During one phase of the study: Metyrapone (pills of 250mg) on full stomach: Day 1 0-1-1, day 2 1-2-2, day 3 2-2-3 day 4 3-3-4 day 5 3-3-4 day 6 3-3-4 day 7 3-3-4 day 8 3-0-0

Metyrapone And Hydrocortisone

Placebo 250 mg Tablets DRUG

During another phase of the study: identical looking placebo pills starting Day 1 0-1-1, day 2 1-2-2, day 3 2-2-3 day 4 3-3-4 day 5 3-3-4 day 6 3-3-4 day 7 3-3-4 day 8 3-0-0

Placebo

Hydrocortisone 19,9mg s.c., pulsatile with a flow rate of 10μl/s DRUG

Hydrocortisone will be delivered subcutaneously via a pump in a pulsed fashion with a flow rate of 10μl/s from day 1 to day 8 in a total daily dose of 19.9mg

Metyrapone And Hydrocortisone

Placebo (0,9% NaCl solution) DRUG

Placebo (0,9% NaCl solution) 19.9 mg/d subcutaneously via a pump in a pulsed fashion with a flow rate of 10μl/s from day 1 to day 8

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Since hormone fluctuations associated with the menstrual cycle may alter cortisol levels, women will not be included in the study. Although diversity will be reduced and the statements of the study cannot be applied to the female sex, these strict inclusion criteria allow an optimal homogeneity and increase statistical power.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• BMI 18.5 - 25 kg/m2

You may not qualify if:

• Previous medical history for any chronic condition in the last three months, active disease or abnormal physical examination as verified by a qualified physician.
• Casual smoking (\>6 cigarettes per day)
• Frequent, heavy alcohol consumption (\>30g/day)
• Frequent, heavy caffeine consumption (\>4 caffeinated drinks/day)
• Regular physical exercise (\>4hrs per week)
• Shift workers
• Participation in an investigational drug trail within the past two months
• Intake of any drugs (prescribed, over the counter or recreational) including topical steroids and inhalers, within 48 hours of the study initiation
• Known allergy to metyrapone
• Inability or unwillingness to provide informed consent

Sponsors & Collaborators

• Eleonora Seelig: lead

Study Sites (1)

University Hospital Basel

Basel, Canton of Basel-City, 4031, Switzerland

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Metyrapone

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Placebo-controlled
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Double-blind, randomized, placebo-controlled cross-over study

Study Record Dates

• First Submitted: December 8, 2021
• First Posted: December 22, 2021
• Study Start: February 8, 2022
• Primary Completion: June 8, 2023
• Study Completion: June 8, 2023
• Last Updated: August 23, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)