Characterization of Metabolic and Brain Effects of Rising Glucagon During an Oral Glucose Challenge

Diabetes Clinical Trial

Official title:

Metabolic and Central Nervous System Characterisation of the Phenotype of Non-suppressed (Rising) Glucagon After Glucose Challenge

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03061227
• Other study ID #: 529_2016BO1
• Status: Completed
• Phase: N/A
• Start date: February 10, 2017
• Est. completion date: April 30, 2020

Study information

• Verified date: April 2020
• Source: University Hospital Tuebingen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators previously characterized a phenotype with non-suppressed glucagon at 120 minutes after standardized oral glucose load. This phenotype is associated with healthy metabolic traits such as lower BMI, higher insulin sensitivity and lower liver fat content. Glucagon is a pleiotropic hormone that, besides its main action on increasing endogenous glucose production, also reduces appetite and increases basal energy expenditure. The aims of this study are to i. detect functional differences in the appetite-related central nervous system (CNS) areas between the suppressed and non-suppressed glucagon phenotype ii. mimick the non-suppressed glucagon phenotype in those participants who suppress glucagon by administering a very-low-dose glucagon infusion and retest them.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: April 30, 2020
• Est. primary completion date: January 17, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• BMI 18.5- 29.9 kg/m2

• written informed consent

Exclusion Criteria:

• Current

1. febrile infection with temperatures> 38.5 ° C in the last 14 days

2. Blood donation within the last 12 weeks Pre-study Inclusion

• Chronic diseases:

1. Diabetes mellitus

2. Known liver diseases (hepatitisB/C, hemochromatosis, NASH)

3. Chronic inflammatory diseases (rheumatoid arthritis, Crohn's disease, ulcerative colitis) chronic renal insufficiency

4. Cancer (known malignant disease)

5. psychiatric diagnoses (bipolar disorder, schizophrenia, psychoses, depression, agoraphobia)

6. Persons with non-removable metal parts, e.g:

• pacemaker

• artificial heart valves

• metal prostheses

• implanted magnetic metal parts (screws, plates of operations)

• spiral

• metal slivers / garnet splinters

• fixed braces

• Acupuncture needle

• Insulin pump

• totally implantable venous access device (port)

• tattoos, metallic eye shadows

7. Persons with impaired sensitivity and / or increased sensitivity to heating of the body

8. Medical history of venous thromboembolism

9. alcohol consumption of more than 50g / day

10. In physical examination:

blood pressure > 160/100 mmHg pathologic cardiac murmurs (diastolic or systolic louder than 2/6)

11. in the blood test: fasting glucose = 125 mg/dl or HbA1c = 6.5% AST or ALT> 2.5x upper limit of the reference range (> 125 U/l) Hb <12 g/dl C reactive protein (CRP) > 5 mg / dL or leukocytes> 15000/µl

Related Conditions & MeSH terms

• Diabetes
• Metabolic Syndrome

Intervention

Drug:
• Intravenous glucagon
Randomized application of glucagon or saline during oral glucose tolerance test
• Intravenous saline
Randomized application of glucagon or saline during oral glucose tolerance test

Locations

Country	Name	City	State
Germany	University Hospital Tübingen	Tübingen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Tuebingen

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brain activity	Resting-state brain activity assessed by fMRI	change from baseline to 120 minutes after oral glucose challenge
Secondary	Hunger rating	On visual analogue scale	before and 150 minutes after oral glucose challenge and start of glucagon/saline infusion
Secondary	Brain response to food cues	Assessed by functional magnetic resonance imaging (fMRI)	before, 30 minutes and 120 minutes after oral glucose challenge and start of glucagon/saline infusion
Secondary	Glucose tolerance	Assessed by 75 g oral glucose tolerance test	0-120 minutes
Secondary	Insulin sensitivity	Assessed during 75 g oral glucose tolerance test	0-120 minutes
Secondary	Basal energy expenditure	Assessed by indirect calorimetry	150 minutes after oral glucose challenge
Secondary	Change in hormone levels	Change in adrenocorticotropic hormone (ACTH), growth hormone (GH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), fibroblast growth factor 21(FGF-21) after oral glucose challenge and start of glucagon/saline infusion.	0-150 minutes