Postprandial Profiles of Metabolites and Appetite-regulating Hormones in Plasma and Cerebrospinal Fluid

Overweight and obesity are rising in prevalence and becoming a growing threat to public health. Obesity is associated with an increased all-cause mortality, impaired quality of life, and numerous of disorders. Therapeutic strategies against obesity - which include an abundance of dietary and physical training programmes and pharmaceutical drugs to increase energy expenditure or limit appetite or gastro-intestinal fat absorption - have shown limited success on long term weight loss. Thus, overweight and associated conditions is becoming the new normal and there is a need for better understanding gut-to-brain signalling, hormonal and metabolic disturbances in overweight individuals.

The purpose of this health science research project is to describe the coinciding plasma and cerebrospinal fluid (CSF) profiles of selected biomarkers after co-ingestion of a meal and model pharmaceuticals in patients with overweight and/or type 2 diabetes compared to healthy control individuals.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Diabetes Mellitus, Type 2
• Intervention / Treatment: Other: Large liquid meal, spinal catheter and venous line

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mikkel B Christensen, MD, PhD; Phone Number: +4538635102; Email: Mikkel.bring.christensen@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2400
    • Recruiting
    • Deparrtment of clinical pharmacology
    • Contact: Mikkel B Christensen, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 10 male patients with obesity (BMI >30) and type 2 diabetes
• 10 male volunteers with normal weight (BMI 20-24) matched by age
• 10 male volunteers with obesity (BMI >30) matched by age

Exclusion Criteria:

1. Unwillingness to participate or wish to withdraw from ongoing protocol
2. Hepatic disease or hemorrhagic diatheses (including abnormal International Normalized Ratio (INR), bilirubin, blood levels of thrombocytes, alanine-aminotransferase (ALAT))
3. Anticoagulant treatment (e.g. treatment with warfarin, apixaban or another oral anticoagulant)
4. Anaemia (p-hemoglobin below normal range)
5. Nephropathy (se-creatinine >130 μM and/or albuminuria)
6. Suspected difficult access to the spinal canal (e.g. pronounced scoliosis, spinal stenosis, osteoporotic coincidence in the lower back, spina bifida, meningocele after surgical intervention)
7. Lumbar skin infection (e.g. herpes zoster, pustules or ulcers)
8. Medical history with headaches - both in connection with dura puncture and frequent headaches of other types
9. Central nervous system disease (including dementia, previous stroke, multiple sclerosis, epilepsy, etc.)
10. Clinical suspicion of increased intracranial pressure (headaches, visual disturbances etc.)
11. Patients with type 2 diabetes: Treatment with DPP-4 inhibitor or GLP-1 receptor agonist. Late diabetic complications including proliferative diabetic retinopathy (anamnestic), arteriosclerotic cardiovascular disease (heart failure or previous ischemic event/myocardial infarction)

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
Other: Intervention arm	Other: Large liquid meal, spinal catheter and venous line; Large liquid meal (e.g. Nutricia® Energy 500 ml (750 kcal) admixed paracetamol 1000 mg (for estimation of gastric emptying). Spinal catheter for 4 hours, with samples taken at one hour interval. 2 venous lines, one for saline and one for venous sampling every half hour

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Appetite regulating hormones measured by specific immunoassays	After 1 hour
Appetite regulating hormones measured by specific immunoassays	After 2 hour
Appetite regulating hormones measured by specific immunoassays	After 3 hours
Appetite regulating hormones measured by specific immunoassays	After 4 hours

Other Outcome Measures

Outcome Measure	Time Frame
Metabolomics measured in blood and cerebrospinalfluid using mass spectrometry	After 1 hour
Metabolomics measured in blood and cerebrospinalfluid using mass spectrometry	After 2 hours
Metabolomics measured in blood and cerebrospinalfluid using mass spectrometry	After 3 hours
Metabolomics measured in blood and cerebrospinalfluid using mass spectrometry	After 4 hours
Proteomics measured in blood and cerebrospinalfluid using mass spectrometry	After 1 hour
Proteomics measured in blood and cerebrospinalfluid using mass spectrometry	After 2 hours
Proteomics measured in blood and cerebrospinalfluid using mass spectrometry	After 3 hours
Proteomics measured in blood and cerebrospinalfluid using mass spectrometry	After 4 hours
Peptidomics measured in blood and cerebrospinalfluid using mass spectrometry	After 1 hour
Peptidomics measured in blood and cerebrospinalfluid using mass spectrometry	After 2 hour
Peptidomics measured in blood and cerebrospinalfluid using mass spectrometry	After 3 hours
Peptidomicsmeasured in blood and cerebrospinalfluid using mass spectrometry	After 4 hours

Collaborators and Investigators

• Sponsor: Mikkel Bring Christensen
• Investigators: Principal Investigator: Mikkel.bring.christensen@regionh.dk B Christensen, MD, PhD, Department of clinical pharmacology, Bispebjerg Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2023
• Primary Completion (Estimated): October 5, 2024
• Study Completion (Estimated): October 10, 2024

Study Registration Dates

• First Submitted: October 25, 2023
• First Submitted That Met QC Criteria: October 30, 2023
• First Posted (Estimated): November 3, 2023

Study Record Updates

• Last Update Posted (Estimated): November 3, 2023
• Last Update Submitted That Met QC Criteria: October 30, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: CSF-meal

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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