Experimental hypothermia using cold ambient temperature and drug-induced inhibition of shivering in awake, healthy volunteers: a crossover, double blinded trial

Phase 1

• Conditions: Hypothermia; Therapeutic area: Diseases [C] - Disorders of Environmental Origin [C21]; Therapeutic area: Phenomena and Processes [G] - Physiological processes [G07]

• Registration Number: CTIS2023-506020-81-00
• Lead Sponsor: Helse Bergen HF

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-06-28
• Study Completion: 2023-11-16
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

Participant must be over 18 and under 40 years of age at the time of signing the informed consent., Participants who are overtly healthy as determined by their medical history. The participants will be asked to fill out a health-report stating to be healthy, using no relevant medication, and having no relevant allergies or hypersensitivity to the active substances or to any of the excipients of the IMPs used., BMI under 30 kg/m2, Both male and female participants can be included. Female participants of childbearing potential will be asked to take a pregnancy test to confirm the absence of pregnancy prior to study drug administration on both visit 1 and 2., Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

Exclusion Criteria

Drugs: Concomitant use of sedatives, MAO-inhibitors, SSRI, ritonavir, cimetidin, klorpromazine, fenytoin, erythromycin, itrakonazol, platelet inhibitors, apomorfin, alcohol (during the trial period) or other opioids (during the trial period). A history of drug dependency., Recent head injury, increased ICP, seizures or epilepsy., Other: Known reduced liver- or kidney function, reduced respiratory drive, known supraventricular tachycardia or prolonged QTc, hypertrophy of the prostate or urinary constriction, ongoing pregnancy or breastfeeding. Known acute glaucoma, Myasthenia gravis. Previous abdominal surgery. History of cold injuries or frostbites., Planned MRI the next two days after ingestion of temperature capsule.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: We aim to reduce core temperature by lowering ambient temperature utilizing a climate chamber and administrating meperidine and buspirone to inhibit shivering. We will measure difference in temperature (active drug vs. placebo) at termination.;Secondary Objective: Identify the trajectory of temperature, Inhibition of shivering, Participant safety: Identify respiratory depression, identify circulatory effects, identify sedative effect, measure afterdrop, measure thermal discomfort, pain and nausea, identify toxic concentration of normeperidine, identify hypo-/ hyperglycemia, identify risk of frostbites.;Primary end point(s): Temperature at termination. The experiment for a participant will be terminated if temperature reaches 35C or active cooling exceeds 3 hours or other reasons (technical problems, terminated by participant). Temperature will be measured at all timepoints. Temperature measurements by Body CAP capsule at all time points will function as backup.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Time from initiation of cooling to termination. Esophageal temperature at all time points. Temperature measurements by Body CAP capsule at all time points will function as backup.;Secondary end point(s):Composite score, resulting in shivering present (Yes/No);Secondary end point(s):Respiratory rate, end-tidal pCO2, SpO2, blood pressure, heartrate, ECG, RASS, difference between temperature at termination and lowest temperature measured after extrication from cold exposure, thermal discomfort VAS(0-10), pain VAS (0-10), nausea yes/no (if yes: mild, moderate or severe), concentration of normeperidine at presumed maximum outside reference range, capillary blood glucose outside reference range measured 30 min after extrication from cold exposure, skin temperature <8C.