Intermittent Hypoxia-hyperoxia Conditioning as a New Therapeutic Intervention to Reduce Hypertension (HyperIHHC)

NCT05603676 | Unknown DMC

• 1 other identifier: 2022-01295
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this project is to examine the efficiency of intermittent hypoxia-hyperoxia conditioning (IHHC) protocol to improve vascular health and reduce blood pressure in hypertensive patients (stage 1). The result of the present study will investigate if IHHC could be a therapeutic treatment for hypertensive individuals. The investigation is designed with a placebo intervention (air ambient) and a control group (age-matched healthy participants). The interest of short cycles of intermittent hypoxia-hyperoxia is due to the triggering of the vasodilatory response in a greater extent compared to the pressor mechanisms since the exposure duration remains short. Therefore, it can be hypothesized that control and hypertensive groups achieving IHHC may exhibit a decreased blood pressure compared to the control and hypertensive groups achieving placebo intervention. The control group may show greater change than hypertensive due to higher vascular reserve. The secondary objective of the study is to understand the underlying mechanism of the beneficial effects of IHHC, especially the role of blood hemorheological changes. Based on available literature, it is know that hypoxia induce an increase in blood viscosity. One may hypothesize that with such a short hypoxic dose used during IHHC, only minor change in blood viscosity may occur. However, a slight rise in blood viscosity is known to stimulate NO synthase and then to produce more NO. Hence it could be one of the mechanisms involved in the early vasodilatory response to hypoxia. These findings are in line with the reported higher NO end-product metabolites during exercise in normoxia and hypoxia in subjects who showed a rise in blood viscosity after exercise. The hypothesis is that the magnitude of IHHC beneficial effects is related to change in blood viscosity and its determinants.

Conditions

Hypertension

Keywords

Intermittent hypoxia-hyperoxia conditioning; Vascular function; Hemorheology

Outcome Measures

Primary Outcomes (1)

• 24 hours Blood pressure change form pre to post intervention

  a major risk factor, when too high, for cardiovascular diseases will be continously measured for 24 hours.

  One week before the intervention and one week after the intervention

Secondary Outcomes (15)

• Baroreflex sensitivity

  One week before the intervention and one week after the intervention

• Reactive hyperemia index

  One week before the intervention and one week after the intervention

• Vascular occlusion test (VOT)

  One week before the intervention and one week after the intervention

• Pulse wave velocity

  One week before the intervention and one week after the intervention

• Cerebrovascular reactivity to carbon dioxide (CO2)

  One week before the intervention and one week after the intervention

Study Arms (4)

Hypertensive IHHC

EXPERIMENTAL

Hypertensive participants who performed IHHC

Other: Intermittent hypoxia-hyperoxia conditioning

Hypertensive placebo

PLACEBO COMPARATOR

Hypertensive participants who performed placebo intervention

Other: Placebo intervention

Healthy IHHC

ACTIVE COMPARATOR

Healthy participants who performed IHHC

Other: Intermittent hypoxia-hyperoxia conditioning

Healthy Placebo

SHAM COMPARATOR

Healthy participants who performed placebo intervention

Other: Placebo intervention

Interventions

Intermittent hypoxia-hyperoxia conditioning OTHER

The IHHC protocol consist of 6 bouts of 6 min breathing hypoxia (FiO2 = 11.5%) following by 3 min breathing hyperoxia (FiO2 = 31.5%) (Figure 2). The total duration of a session is 54 minutes. Participant will undergo 3 session a week for 6 weeks. During the session, participant will be comfortably seated on an armchair and equipped with a mask and a non-rebreathing valve rely to a motorized valve that blindly change the gas input from two different mixing chambers with hypo and hyperoxic gas mixture. Participants will be instructed to relax and breath normally throughout the session.

Healthy IHHC; Hypertensive IHHC

Placebo intervention OTHER

Placebo intervention will be like the IHHC protocol but with mixing chambers full of ambient air. The total duration of a placebo session is 54 minutes. Participant will undergo 3 session a week for 6 weeks. During the session, participant will be comfortably seated on an armchair and equipped with a mask and a non-rebreathing valve rely to a motorized valve that blindly change the gas input from two different mixing chambers with ambient air. Participants will be instructed to relax and breath normally throughout the session.

Healthy Placebo; Hypertensive placebo

Eligibility Criteria

• Age: 44 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• to be aged between 44 and 65 years old.
• for women, post-menopausal will be considered.
• for hypertensive group, stage 1 hypertension: systolic blood pressure (140-159 mmHg) and/or diastolic blood pressure (90-99 mmHg).
• free of other disease than hypertension and free of anti-hypertensive treatment medication.
• Hypertensive participants with 14 days of hypertensive drugs wash-out.
• able to complete all sessions.
• able to give consent.

You may not qualify if:

• Peripheral arterial disease
• Atrial fibrillation
• Hypoxic congenital heart diseases
• Pulmonary Hypertension
• using dietary supplements or drugs which interfere with the measurements (nitrate supplementation)

Sponsors & Collaborators

• Gregoire Millet: lead
• Centre Hospitalier Universitaire Vaudois: collaborator

Study Sites (1)

ISSUL

Lausanne, Canton of Vaud, 1015, Switzerland

Location

Related Publications (3)

• Lyamina NP, Lyamina SV, Senchiknin VN, Mallet RT, Downey HF, Manukhina EB. Normobaric hypoxia conditioning reduces blood pressure and normalizes nitric oxide synthesis in patients with arterial hypertension. J Hypertens. 2011 Nov;29(11):2265-72. doi: 10.1097/HJH.0b013e32834b5846.

  PMID: 21897291 BACKGROUND

• Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, Chalmers J, Rodgers A, Rahimi K. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016 Mar 5;387(10022):957-967. doi: 10.1016/S0140-6736(15)01225-8. Epub 2015 Dec 24.

  PMID: 26724178 BACKGROUND

• Serebrovskaya TV, Xi L. Intermittent hypoxia training as non-pharmacologic therapy for cardiovascular diseases: Practical analysis on methods and equipment. Exp Biol Med (Maywood). 2016 Sep;241(15):1708-23. doi: 10.1177/1535370216657614. Epub 2016 Jul 12.

  PMID: 27407098 BACKGROUND

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Grégoire P Millet, PhD

  University of Lausanne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Grégoire P Millet, PhD

CONTACT

021 692 32 94; gregoire.millet@unil.ch

Antoine Raberin, PhD

CONTACT

0216923796; antoine.raberin@unil.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Single-blinded means that participants will not be inform than a half will follow a placebo intervention.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate professor

Model Details: This project is a single center national study. It is designed as a randomized single-blinded parallel group control study. Single-blinded means that participants will not be inform than a half will follow a placebo intervention. Parallel group means that the design serves to compare different experimental conditions. Randomized means that the participants are assigned to the two different conditions randomly (by chance alone). Control means that one of the group/conditions is the standard of comparison (control participant achieving placebo and IHHC interventions). A follow-up, one month after the intervention will be done.

Study Record Dates

• First Submitted: September 20, 2022
• First Posted: November 3, 2022
• Study Start: November 15, 2022
• Primary Completion: May 15, 2023
• Study Completion: May 15, 2023
• Last Updated: November 3, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)