Optimization Strategy for the Prevention of AMS by RIPC Combined With Acetazolamide

Optimization Strategy for the Prevention of Acute Mountain Sickness by Remote Ischemic Preconditioning Combined With Acetazolamide

The primary objective of the study will be to determine whether rapid remote limb ischemic preconditioning (RIPC) combined with acetazolamide can further reduce the incidence of acute mountain sickness (AMS) during the 6-hour hypoxic chamber.

Study Overview

• Status: Completed
• Conditions: Acute Mountain Sickness
• Intervention / Treatment: Drug: Acetazolamide; Device: Doctormate® (twice daily for 6 days); Device: Doctormate® (forth daily for 3 days)

Detailed Description

The current measures to prevent acute mountain sickness (AMS) mainly include drug prevention and non-drug prevention. Acetazolamide is a drug approved by the U.S. FDA for the prevention and treatment of AMS. Remote limb ischemic preconditioning (RIPC) can also reduce the incidence of AMS as a non-durg method, with a strategy of 2 times/day training for 1 week reducing the incidence of AMS in 6 hours from 40% to 30%. The objective of this study is to determine whether rapid RIPC training combined with acetazolamide can further reduce the incidence of AMS. In this study, subjects will be divided into 5 groups: medicine group (acetazolamid 125mg bid, 2 days before entering the hypoxic room), RIPC group (RIPC training twice daily, 6 days before entering the hypoxic room), rapid RIPC group (RIPC training forth daily, 3 days before entering the hypoxic room), combined group (rapid RIPC training plus acetazolamide) and controlled group. RIPC training, completed by Renqiao Remote Ischemic Conditioning Device (Doctormate®), will be comprised of 5 cycles of bilateral upper limb ischemia and reperfusion, which will be induced by 2 cuffs placed around the upper arms respectively and inflated to 200mmHg for 5 minutes followed by 5 minutes of reperfusion by cuff deflation. After the intervention, subjects will be exposed to 4500m altitude in a normobaric hypoxic chamber for 6 hours. The incidence of AMS and other data will be compared between groups.

• Study Type: Interventional
• Enrollment (Actual): 252
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Xuanwu Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• People who live in plain areas all year round and have not been to an altitude of 1500 meters or more in the past 30 days;
• Sign the informed consent form voluntarily.

Exclusion Criteria:

• Chronic physical or mental diseases, including hypertension, diabetes, coronary heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, migraine, anxiety, depression, insomnia, etc.;
• The female is pregnant or in the period of preparing for pregnancy or breast-feeding;
• Have a history of smoking;
• Have a history of thrombosis in the upper limbs;
• Severe damage to local soft tissues of upper limbs, fractures, etc.;
• Allergic to sulfa;
• Are taking one or more drugs;
• Past laboratory tests suggest hypokalemia, hyponatremia, or liver and kidney damage;
• Patients unsuitable for enrollment in the clinical trial according to investigators decision making.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Medicine Group; Start orally take Acetazolamide 2 days before entering the hypoxic room.	Drug: Acetazolamide; Start orally take acetazolamide 125mg twice daily, 2 days before entering the hypoxic chamber. Subjects will enter the hypoxic room at 9am on the third day. At that time, the subject should have taken the drug 5 times.
ACTIVE_COMPARATOR: RIPC Group; Start RIPC training twice daily, 6 days before entering the hypoxic room.	Device: Doctormate® (twice daily for 6 days); Start RIPC training twice daily, 6 days before entering the hypoxic chamber. RIPC will be induced by Renqiao Remote Ischemic Conditioning Device (Doctormate®). Each training will be comprised of 5 cycles of bilateral upper limb ischemia and reperfusion, which will be induced by 2 cuffs placed around the upper arms respectively and inflated to 200mmHg for 5 minutes followed by 5 minutes of reperfusion by cuff deflation. Subjects will enter the hypoxic room at 9am on the seventh day. At that time, the subject should have finished 13 times of RIPC training.
EXPERIMENTAL: Rapid RIPC Group; Start RIPC training forth daily, 3 days before entering the hypoxic room.	Device: Doctormate® (forth daily for 3 days); Start RIPC training forth daily, 3 days before entering the hypoxic chamber. RIPC will be induced by Renqiao Remote Ischemic Conditioning Device (Doctormate®). Each training will be comprised of 5 cycles of bilateral upper limb ischemia and reperfusion, which will be induced by 2 cuffs placed around the upper arms respectively and inflated to 200mmHg for 5 minutes followed by 5 minutes of reperfusion by cuff deflation. Subjects will enter the hypoxic room at 9am on the forth day. At that time, the subject should have finished 13 times of RIPC training.
EXPERIMENTAL: Combined Group; Medicine + Rapid RIPC	Drug: Acetazolamide; Start orally take acetazolamide 125mg twice daily, 2 days before entering the hypoxic chamber. Subjects will enter the hypoxic room at 9am on the third day. At that time, the subject should have taken the drug 5 times.; Device: Doctormate® (forth daily for 3 days); Start RIPC training forth daily, 3 days before entering the hypoxic chamber. RIPC will be induced by Renqiao Remote Ischemic Conditioning Device (Doctormate®). Each training will be comprised of 5 cycles of bilateral upper limb ischemia and reperfusion, which will be induced by 2 cuffs placed around the upper arms respectively and inflated to 200mmHg for 5 minutes followed by 5 minutes of reperfusion by cuff deflation. Subjects will enter the hypoxic room at 9am on the forth day. At that time, the subject should have finished 13 times of RIPC training.
NO_INTERVENTION: Control Group; Subjects do not receive specific interventions before entering the hypoxic room.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of acute mountain sickness.	The diagnosis of acute mountain sickness is based on '2018 Lake Louise Acute Mountain Sickness Score' , 'Acute Mountain Sickness-Cerebral Scores',etc. All subjects should finish the questionnaires to evaluate the total incidence.	6 hours after entering the hypoxic room.
The severity of acute mountain sickness.	The diagnosis of acute mountain sickness is based on '2018 Lake Louise Acute Mountain Sickness Score' , 'Acute Mountain Sickness-Cerebral Scores',etc. All subjects should finish the questionnaires to evaluate the total incidence.	6 hours after entering the hypoxic room.
Fingre pulse oximetry of the subjects.	Fingre pulse oximetry using pocket pulse oximeters will be noted.	6 hours after entering the hypoxic room.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure of the subjects.	Including systolic and diastolic pressure.	6 hours after entering the hypoxic room.
Heart rate of the subjects.		6 hours after entering the hypoxic room.
Respiratory rate of the subjects.		6 hours after entering the hypoxic room.

Collaborators and Investigators

• Sponsor: Ji Xunming,MD,PhD

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2021
• Primary Completion (ACTUAL): August 22, 2022
• Study Completion (ACTUAL): August 30, 2022

Study Registration Dates

• First Submitted: August 15, 2021
• First Submitted That Met QC Criteria: August 20, 2021
• First Posted (ACTUAL): August 27, 2021

Study Record Updates

• Last Update Posted (ACTUAL): October 3, 2022
• Last Update Submitted That Met QC Criteria: September 30, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Acetazolamide; Acute Mountain Sickness; Remote Ischemic Preconditioning
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Altitude Sickness; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide
• Other Study ID Numbers: RIPC-Acet-AMS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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