NCT06739473

Total-body Glucose Utilization in Obesity

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Turku University Hospital · Other Government
• Sex: All
• Age: 20 Years – 60 Years
• Healthy volunteers: Accepted

Summary

There are three goals for this study. One is to investigate how different emotions and exposure to cold affect blood flow in the body. The second aim is to study how insulin affects blood flow and tissue glucose uptake, and to study whether this effect is altered in obesity. Last, the study focuses on establishing the lowest dose of a PET radiotracer, oxygen-15 labelled water, that can be used in clinical studies with a new whole-body PET scanner.

Detailed description

The study consists of two separate parts: the dose escalation study and the part studying the effects of emotions and insulin on blood flow. All participants will first undergo a screening visit starting with signing an informed consent form. Then they will undergo a physical examination, are interviewed about their medical history. Finally, some routine laboratory tests are collected, and a 75 g oral glucose tolerance test is performed. The participants who are eligibile for the study will continue to the PET studies. The dose escalation study will be completed first. In this 8 participants will be studied once with Siemens Biovision Quadra PET/CT scanner. They will receive eight doses of oxygen-15 labelledradiowater (H2\[15O\]O) ranging from 25 to 700 MBq, with each dose repeated twice to evaluate repeatability of each dose. These participants will not undergo any further studies. For the other subjects, there will be two more PET study visits. On the first visit, the effects of emotions, evoked by short movie clips or cold exposure of one leg, on whole-body blood flow will studied with oxygen-15 labelled radiowater. Each participant will be studied 8 times in one session, with repeated H2\[15O\]O boluses of 400 MBq followed by 7.5 min dynamic PET scans with Siemens Biovision Quadra PET/CT scanner and a 5 min recovery and wash-out period. On the other visit the effects of insulin on circulation will be studied by performing a hyperinsulinemic, euglycemic clamp during the PET scan. During the clamp, fast-acting insulin (NovoRapid, NovoNordisk) is administered intravenously at a fixed rate (40 mU/m2 body surface area/min). Plasma glucose is monitored every 5-10 minutes, and 20 % glucose is administered at a varying rate to maintain euglycemia (5.0 mmol/L). At the scanner a fasting H2\[15O\]O PET/CT scan (400 MBq) will be performed first. After this, the hyperinsulinemic, euglycemic clamp is started, and the radiowater scans are repeated 10 minutes and 50 minutes into the insulin infusion. 60 minutes after the start of clamp, 100 MBq of glucose analogue tracer \[18F\]fluorodeoxyglucose is administered and a 50 min dynamic PET scan is started. After the scan, insulin infusion is discontinued and participants are monitored until plasma glucose levels are adequate for safe discharge. For a subgroup of participants, skeletal muscle microvascular bloodflow will also be assessed with contrast-enhanced ultrasound performed during fasting and 30 minutes after the start of clamp. The participants will be administered intravenous contrast agent, and after steady plasma concentration is reached (2.5 min), the contrast agent micro bubbles are destroyed with a high-intensity ultrasound signal, and the rate at which small arterioles are refilled is measured. Data will be analysed using in-house developed programs. Regions of interest will be drawn manually for peripheral tissues (skeletal muscle, visceral, brown and subcutaneous adipose tissue, liver, kidney, intestines) and using automated segmentation tools for the brain.

Conditions

• Obesity and Overweight

Interventions

Type	Name	Description
BEHAVIORAL	Movies	Participants will watch eight short movie clips, and the changes different emotions evoked by the clips will be studied using H2\[15O\]O PET/CT.
BEHAVIORAL	Cold	Participants will be studied with H2\[15O\]O PET/CT while one of their legs will be exposed to cold to study the effects of cold stimulus on whole-body blood flow.
DRUG	Hyperinsulinemic euglycemic clamp	Participants will be administered intravenous fast acting insulin (NovoRapid, Novo Nordisk, 1 mU/m2 body surface area/min) together with 20 % glucose to maintain normal glucose values (5.0 mmol/L) to study the effects of insulin on whole body blood flow with H2\[15O\]O PET/CT, and to assess tissue insulin-stimulated glucose uptake with \[18F\]FDG PET/CT.
RADIATION	H2[15O]O PET/CT	H2\[15O\]O PET/CT, with a dose of 25-700 MB/bolus repeated 2-8 times per scan.
RADIATION	[18F]FDG PET/CT	Whole-body \[18F\]FDG PET/CT scan to study tissue glucose uptake, dose 100 MBq
DRUG	CEUS or Contrast enhanced Ultrasound	Contrast-enhanced ultrasound of left forearm muscles is performed during fasting and after 30-40 minutes of hyperinsulinemia

Timeline

• Start date: 2023-01-25
• Primary completion: 2024-12-01
• Completion: 2024-12-01
• First posted: 2024-12-18
• Last updated: 2024-12-18

Locations

1 site across 1 country: Finland