The Role of Glucocorticoids to Maintain Energy Homeostasis During Starvation (Gluco-Starve)

NCT05919992 | Completed Early Phase 1

• 1 other identifier: EKNZ 2022-01837
• Study Type: interventional
• Target: 24
• 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 fasting periods with each treatment. With the block and replace therapy, fasting-induced GC peak will be suppressed. Metabolic and autonomic parameters will be compared to reveal whether GCs mediate the physiological adaptions to caloric restriction. Understanding acute effects of GCs upon caloric restriction is critical, since repetitive disruptions of GC secretion may become harmful in chronic conditions.

Conditions

Glucocorticoid Effect

Keywords

cortisol; glucocorticoids; starvation; caloric restriction; fasting

Outcome Measures

Primary Outcomes (1)

• Satiation

  Amount of food intake with ad libitum buffet

  Two 7-day intervention periods

Secondary Outcomes (19)

• Satiety

  Two 7-day intervention periods

• Food preference

  Two 7-day intervention periods

• Energy expenditure

  Two 7-day intervention periods

• Substrate utilization

  Two 7-day intervention periods

• Blood pressure

  Two 7-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 3000mg/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 empty stomach: Day 1 0-1-1, day 2 1-2-2, day 3 2-3-3 day 4 3-4-4 day 5 4-4-4 day 6 4-4-4 day 7 4-0-0

Metyrapone And Hydrocortisone

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 7 in a total daily dose of 19.9mg

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 2-3-3 day 4 3-4-4 day 5 4-4-4 day 6 4-4-4 day 7 4-0-0

Placebo

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 7

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• BMI 18.5 - 27 kg/m2
• Weight stability for 6 months prior to the trial (+/- 2kg)

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 trial within the past two months
• Intake of any drugs (prescribed, over the counter or recreational), within 48 hours of the study initiation
• Intake of any steroids (including topical or inhaler) six month prior to the study
• Known allergy to metyrapone or hydrocortisone
• 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

Starvation; Fasting

Interventions

Metyrapone; Hydrocortisone

Condition Hierarchy (Ancestors)

Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

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: March 3, 2023
• First Posted: June 27, 2023
• Study Start: May 15, 2023
• Primary Completion: July 25, 2024
• Study Completion: July 25, 2024
• Last Updated: August 14, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)