Investigating the Acute Effects of Increasing Alanine Exposure in Healthy Participants

Investigating the Effect of Glucagon on Cognitive Function and Cerebral Glucose Metabolism in Humans: A Pilot Study

In this study the investigators will investigate the acute effects of increasing alanine exposure on metabolic parameters in healthy participants.

Participants will participate in one study day. After initial baseline blood samples, a three-hour intravenous infusion with glucagon will be initiated. The infusion rate will be increased every 30 minutes.

Study Overview

• Status: Not yet recruiting
• Conditions: Glucose Metabolism; Glucagon
• Intervention / Treatment: Other: alanine

Detailed Description

Two peripheral catheters will be placed in the antecubital vein of each arm for infusion of L-alanine and blood sampling respectively. The infusion rate of alanine will start at 1.4 μmol/kg/min and increase every 30 minutes over a 3-hour period, up to a maximum of 28 μmol/kg/min. The study day will last approximately 4 hours, and a maximal blood volume of 130 ml will be collected. Blood samples for the analysis of plasma glucagon, glucose, insulin, C-peptide etc. will be drawn every 15 minutes.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elvar Már Sturlaugsson Jóhönnuson, Stud. Med.; Phone Number: 21205944 Ext. 0045; Email: elvar.mar.sturlaugsson@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Department of Clinical Biochemistry, Copenhagen University Hospital - Bispebjerg and Frederiksberg
    • Contact: Sophie BB Johnsen, MD; Phone Number: 004521205944; Email: sophie.betty.brock.johnsen.01@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Capable of understanding the participant information and signing the consent form
• Between 25 and 70 years of age at the time of screening
• Body mass index (BMI) ≤ 25 kg/m2 at the time of screening

Exclusion Criteria:

• Enrolment in other research projects that might interfere with the study
• Diabetes diagnosis (type 1 and 2)
• Pregnancy or breastfeeding
• Use of medications which, in the opinion of the investigator, may jeopardise participant's safety or compliance with the protocol
• Impaired liver function defined as either alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) ≥ 2 times normal values
• Kidney disease defined as serum creatinine levels ≥ 126 μmol/L for male and ≥ 111 μmol/L for female
• Inadequately treated blood pressure at screening defined as repeated resting blood pressure outside the range 90-150 mmHg for systolic and 50-100 mmHg for diastolic
• Active or recent malignant disease
• Current or history of severe alcohol use or drug/chemical abuse as per investigator's judgement
• Any chronic disorders or severe diseases which, in the opinion of the investigator, might jeopardise participant's safety or compliance with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alanine infusion	Other: alanine; A three-hour intravenous infusion with alanine with increasing infusion rate (from 1.4 μmol/kg/min and to 28 μmol/kg/min)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Threshold alanine infusion rate for stimulation of plasma glucagon	Lowest alanine infusion rate (µmol/kg/min) at which plasma glucagon concentration is significantly higher than baseline during a 3-hour stepwise alanine infusion (six 30-minute steps from 1.4 to 28 µmol/kg/min).	Baseline and every 30 minutes during the 0-180 min infusion period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma glucose during stepwise alanine infusion	Plasma glucose concentration (mmol/L) measured at baseline and every 30 minutes during a 3-hour stepwise alanine infusion (1.4-28 µmol/kg/min), analyzed as absolute values and change from baseline.	Baseline and every 30 minutes during the 0-180 min infusion period.
Change in plasma follicle-stimulating hormone (FSH) during stepwise alanine infusion	Plasma follicle-stimulating hormone (FSH) concentration (IU/L) measured at baseline and at the end of the 3-hour stepwise alanine infusion to explore acute effects on pituitary gonadotropin secretion.	Baseline and every 30 minutes during the 0-180 min infusion period.
Change in plasma luteinizing hormone (LH) during stepwise alanine infusion	Plasma luteinizing hormone (LH) concentration (IU/L) measured at baseline and at the end of the 3-hour stepwise alanine infusion to explore acute effects on pituitary gonadotropin secretion.	Baseline and every 30 minutes during the 0-180 min infusion period.
Change in plasma cortisol during stepwise alanine infusion	Plasma cortisol concentration (nmol/L) measured at baseline and every 60 minutes during the 3-hour stepwise alanine infusion to assess activation of the hypothalamic-pituitary-adrenal axis.	Baseline and every 30 minutes during the 0-180 min infusion period.
Change in plasma triglycerides during stepwise alanine infusion	Plasma triglyceride concentration (mmol/L) measured at baseline and at the end of the 3-hour stepwise alanine infusion to evaluate acute effects on lipid metabolism.	Baseline and every 30 minutes during the 0-180 min infusion period.
Change in plasma urea during stepwise alanine infusion	Plasma urea (carbamide) concentration (mmol/L) measured at baseline and at the end of the 3-hour stepwise alanine infusion to assess short-term effects on nitrogen metabolism.	Baseline and every 30 minutes during the 0-180 min infusion period.
Change in plasma alanine aminotransferase (ALAT) during stepwise alanine infusion	Plasma alanine aminotransferase (ALAT/ALT) activity (U/L) measured at baseline and at the end of the 3-hour stepwise alanine infusion to assess acute changes in liver enzyme levels.	Baseline and every 30 minutes during the 0-180 min infusion period.
Change in plasma C-peptide during stepwise alanine infusion	Plasma C-peptide concentration (pmol/L) measured at baseline and every 30 minutes during a 3-hour stepwise alanine infusion, analyzed as absolute values and change from baseline.	Baseline and every 30 minutes during the 0-180 min infusion period.
Change in plasma insulin during stepwise alanine infusion	Plasma insulin concentration (pmol/L) measured at baseline and every 30 minutes during a 3-hour stepwise alanine infusion, analyzed as absolute values and change from baseline.	Baseline and every 30 minutes during the 0-180 min infusion period.

Collaborators and Investigators

• Sponsor: Nicolai Jacob Wewer Albrechtsen
• Investigators: Principal Investigator: Nicolai Jacob Wewer Albrechtsen, MD PhD, Department of Clinical Biochemistry, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark

Study record dates

Study Major Dates

• Study Start (Estimated): January 20, 2026
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): January 20, 2027

Study Registration Dates

• First Submitted: January 9, 2026
• First Submitted That Met QC Criteria: January 9, 2026
• First Posted (Actual): January 20, 2026

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 9, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: glucagon; glucose metabolism; Alanine
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Amino Acids; Alanine
• Other Study ID Numbers: GluCoMet_stepwise alanine

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No