Calcitonin Gene-related Peptide Antibody in Acute Mountain Sickness

NCT07653516 | Not Yet Recruiting Phase 4

• 1 other identifier: CGRP-Antibody in AMS
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Acute mountain sickness (AMS) is a common condition that can occur when healthy people travel quickly to high altitude. Typical symptoms include headache, nausea, tiredness, dizziness, and poor sleep. In most cases, AMS improves with rest and by not climbing higher, but it can make mountaineering difficult and, in severe cases, can lead to dangerous complications. The biological mechanisms that cause high-altitude headache and AMS are not yet fully understood. Some symptoms of AMS are similar to migraine, suggesting that both conditions may share common pathways in the nervous system. One possible pathway involves calcitonin gene-related peptide (CGRP), a substance known to play an important role in migraine. Fremanezumab is an approved monoclonal antibody used to prevent migraine. It works by binding to CGRP and reducing its biological activity. This study will investigate whether a single dose of fremanezumab can also help prevent symptoms of AMS and high-altitude headache in healthy adults exposed to high altitude. To date, there are no clinical data on the effect of fremanezumab in AMS or high-altitude headache. This is a prospective, randomized, double-blind, placebo-controlled, parallel-group clinical trial. A total of 30 healthy adult volunteers will participate. Participants will be randomly assigned in a 1:1 ratio to receive either a single subcutaneous injection of fremanezumab 225 mg or placebo (saline). Neither the participants nor the investigators will know which treatment was given during the study. The study medication will be administered 1 week before ascent to Capanna Regina Margherita at 4554 meters above sea level. Participants will remain there for 46 hours under hypobaric hypoxic conditions. The main goal is to determine whether fremanezumab reduces the severity of AMS compared with placebo. AMS symptoms will be measured using the Lake Louise Score, a standard questionnaire commonly used in altitude medicine. Additional assessments will include the incidence of AMS, headache characteristics, safety outcomes, vital signs, oxygen saturation, and the use of rescue medication. Symptoms will be assessed repeatedly during the high-altitude stay. Only healthy adults aged 18 to 60 years living below 1000 meters will be eligible. People with important medical conditions, chronic headache or migraine, relevant cardiovascular or lung disease, pregnancy, or recent high-altitude exposure will be excluded. Participants will be closely monitored during the study. Rescue medication, oxygen, and descent to lower altitude will be available if needed. This study may help improve understanding of how AMS develops and whether CGRP blockade could become a new preventive strategy for high-altitude headache and AMS. It may also improve understanding of links between altitude-related headache and migraine.

Conditions

Acute Mountain Sickness

Keywords

acute mountain sickness; calcitonin gene-related peptide antibody; migraine

Outcome Measures

Primary Outcomes (1)

• Severity of acute mountain sickness as measured by the Lake Louise Score (LLS)

  The Lake Louise Score is a validated symptom-based scoring system used to assess acute mountain sickness (AMS). It evaluates the presence and severity of typical AMS symptoms, including headache, gastrointestinal symptoms, fatigue or weakness, dizziness or light-headedness, and sleep disturbance. Each symptom is rated on a scale from 0 to 3, where 0 indicates absence of the symptom and 3 indicates severe symptoms. The total score ranges from 0 to 15, with higher scores indicating more severe AMS symptoms. In this study, the Lake Louise Score will be used to assess the incidence and severity of acute mountain sickness during exposure to high altitude. AMS is typically defined as the presence of headache together with a total Lake Louise Score of 3 or higher.

  after 7, 22, 31, and 46 hours of exposure to hypobaric hypoxia at an altitude of 4,554 m

Secondary Outcomes (1)

• Incidence of acute mountain sickness

  after 7, 22, 31, and 46 hours of exposure to hypobaric hypoxia at an altitude of 4,554 m

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

CGRP antibody

ACTIVE COMPARATOR

Drug: Fremanezumab 225 Mg/1.5 mL Subcutaneous Solution

Interventions

Fremanezumab 225 Mg/1.5 mL Subcutaneous Solution DRUG

Intervention: Fremanezumab Single-dose subcutaneous fremanezumab 225 mg administered 7 days before ascent to high altitude (4554 m) for prevention of acute mountain sickness.

CGRP antibody

Placebo DRUG

Placebo Comparator: Placebo Single-dose subcutaneous placebo (1.5 mL 0.9% saline solution) administered 7 days before ascent to high altitude (4554 m).

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-60 years
• No relevant previous illnesses in the preliminary examination
• Written consent to participate in the study
• Permanent residence \<1000 m
• Men and women are included without prioritization
• Negative urine pregnancy test if pregnancy cannot be ruled out with certainty

You may not qualify if:

• Intolerance / allergy to Fremanzeumab or other drug components
• Acute or chronic lung disease
• Blood pressure systolic ≥150 mmHg or diastolic ≥95 mmHg (average of two measurements) in subjects with or without blood pressure medication
• Pre-existing cardiovascular diseases other than arterial hypertension (coronary heart disease, heart failure, pulmonary hypertension, atrial fibrillation, peripheral arterial occlusive disease)
• Chronic headache, migraine
• Diabetes mellitus
• Smoking (\>6 cigarettes/d) or equivalent nicotine substitution
• Alcohol (\>30 g/d) or other drug abuse
• Overweight (BMI \>30 kg/m2)
• Other pre-existing conditions considered relevant by the investigators (liver disease, kidney disease, thyroid disease, Parkinson's disease, pheochromocytoma)
• Stay \>2000 m altitude within the last 8 weeks before the first study day
• Medication taken within the last 2 months before the first study day, which could influence the data quality (e.g. corticosteroids) or the safety of the subjects (e.g. anticoagulation).
• Blood donation within the last 2 months before the first study day
• Pregnancy or breastfeeding
• Participation in other clinical studies

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Bern University Hospital

Bern, 3010, Switzerland

Location

MeSH Terms

Conditions

Altitude Sickness; Migraine Disorders

Interventions

fremanezumab

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Jürgen Knapp

CONTACT

+41 31 632 77 93; juergen.knapp@insel.ch

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2026
• First Posted: June 17, 2026
• Study Start (Estimated): June 1, 2027
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: July 1, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)