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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Helse Bergen HF

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Disorders of Environmental Origin [C21], Phenomena and Processes [G] - Physiological processes [G07]

Trial duration

1 Oct 2023 → 16 Nov 2023

Decision date (initial)

2023-09-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

The Norwegian Air Ambulance Foundation

External identifiers

EU CT number

2023-506020-81-00

WHO UTN

U1111-1293-7821

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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 objectives 3

1. Identify the trajectory of temperature
2. Inhibition of shivering
3. 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.

Conditions and MedDRA coding

Hypothermia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Participant must be over 18 and under 40 years of age at the time of signing the informed consent.
2. 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.
3. BMI under 30 kg/m2
4. 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.
5. 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 4

1. 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.
2. Recent head injury, increased ICP, seizures or epilepsy.
3. 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.
4. Planned MRI the next two days after ingestion of temperature capsule.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 3

1. 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.
2. Composite score, resulting in shivering present (Yes/No)
3. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Helse Bergen HF

Sponsor organisation

Helse Bergen HF

Address

Haukelandsveien 22

City

Bergen

Postcode

5021

Country

Norway

Scientific contact point

Organisation

Helse Bergen HF

Contact name

Ane Helland

Public contact point

Organisation

Helse Bergen HF

Contact name

Ane Helland

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications