Effects of Acute Intermittent Hypoxia on Brain Function Imaging and Systemic Inflammation

April 7, 2019 updated by: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Effects of acute intermittent hypoxia on brain function imaging and systemic inflammation

Patients with obstructive sleep apnea (OSAS) may have neurological cognitive impairment. The reason is not clear. Intermittent hypoxia is one of the main manifestations of OSAS.

The investigators hypothesize that acute intermittent hypoxia (AIH) can lead to abnormal metabolic activity in some regions of the brain, which may be associated with systemic inflammation.

The investigators proposed in 12 to 15 cases of healthy volunteers, in the form of breathing in the nitrogen intermittently, were observed before and after AIH MRI diffusion tensor imaging (DTI) changes in brain regions and at the same time understand the inflammatory factors and the change of oxidative stress in the human body.

The investigators look at the data from different brain regions of the brain DTI anisotropic score (FA), radial diffusion coefficient (RD), axial diffusion coefficient (AD) and peripheral blood interleukin-6 (IL - 6), interleukin-8 (IL - 8), interleukin-10(IL - 10), tumor necrosis factor alpha (TNF-α), Interleukin-1 beta (IL-1β), Leptin, high sensitivity reactive protein‭‬‬‬‬(hsCRP), Intercellular Adhesion Molecule 1(ICAM 1),Vascular cell adhesion protein 1(VCAM-1) , E-selectin, endothelin-1(ET - 1), 8-iso-PGF2α,3-nitrotyrosine(3-NT),hypoxia-inducible factor 1α(HIF 1α).

Statistical data processing includes: the matching t test of the above indicators before and after AIH; The relationship between DTI and peripheral blood inflammatory factors was analyzed by single factor. Using DTI as the dependent variable, the peripheral blood inflammatory factor was analyzed by multifactor correlation.

Ultimately, the effect of AIH on the brain's regional functions will be understood, and whether the effect is related to systemic inflammation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In this study, the potential risks to subjects and their corresponding prevention measures:

  1. During the test, the volunteers may feel mild sleepiness due to oxygen. (Countermeasures: the subjects have a rest in bed, avoid activity, carry out the whole-process pulse oxygen and heart-rate blood pressure monitoring, and have the full care of the practicing physician)
  2. Venous blood is extracted pre- and post-test, and a few subjects may have halo bloody phenomenon. (Countermeasures: inform, select and remove the halo blood volunteers prior to test.)
  3. During the test, two MRI scans were performed and each was 20 minutes; the duration was longer than the general MRI (no risk).

Judging criteria for adverse events： According to researchers' own experiment, the low oxygen state had no adverse effects on the body or had only slight fatigue and somnolence, which could be improved after inhaling oxygen.

Plan to recruit and enroll 15 healthy volunteers Group time: March 2018 to March 2019 Follow-up time: the last volunteer was followed up for 1 month after completing the test.

Testing method：

  1. Smoking, alcohol drinking, overeating, staying up late were all prohibited one week before the test.

  2. The recruiter came to the test center on the testing morning, and the blood was extracted to check the following: blood routine, hsCRP, blood IL-6, IL-8, TNF-α, IL-1β, leptin , ICAM-1, VCAM-1, E-selectin, ET-1, etc.

    The doctor will check volunteers' EKG as well as their blood pressure, heart rate, respiration rate, blood oxygen saturation (when inhaling air). The first DTI was scanned and also process their dataset.

  3. Then, the test formally started and immediately entered the intermittent hypoxia cycle: With a mouth-nose mask, which can adjust the proportion of nitrogen and oxygen, the doctor could monitor the blood oxygen saturation; through increasing the suction nitrogen concentration, the subject's blood oxygen saturation could decrease to 80%~90% within 30 seconds and also lasts 30 seconds; then quickly reduce the concentration of nitrogen gas suction to make the subject's blood oxygen saturation gradually return to normal level (consistent with the air inhalation), and then continue breathing air about 60 seconds to enter the next round of hypoxic state.

Through adjusting the inhaled nitrogen concentration in patients, the patients could be simulated as the OSA patients who had intermittent hypoxic state due to upper airway collapse at night. This process is equivalent to AIH 25-30 times/h, which is clinically intermediate to severe OSA.

The subjects always keep quiet and undisturbed during the experiment. The low oxygen cycle totally lasted six hours.

4．Subsequently, the subjects repeated the relevant blood tests (Experiment 2) and related checks, and accepted the second DTI scan for comparison with the first scan.

All blood samples in the test are backup. If the testing results appeared obvious abnormality, they can be reviewed immediately. The MRI examination before and after hypoxia was completed on the same day of the test and immediately uploaded to the imaging system, so there would be no data loss. If the subjects felt uncomfortable during the test, they could quit the test at any time. The investigators will re-recruit new qualified participants to carry out the test.

Statistical data processing includes: (1) the paired t-test with the above indicators pre- and post-AIH; (2) the relationship between DTI measures and peripheral blood inflammatory factors by single factor analysis. (3) Using DTI as the dependent variable and the peripheral blood inflammatory factor as the independent variable, multifactor correlation was analyzed.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy volunteers between 18 and 50 years old, no physical abnormalities
  • Without both smoking and drinking habits
  • Without the following symptoms: heart, lung, liver, kidney, and thyroid diseases; neuropsychiatric disorders, diabetes history; histories of craniocerebral surgery and tumor disease; recent acute infectious disease (2 weeks); diseases of chronic systemic infection and inflammation
  • BMI index in the normal range
  • Without snoring and sleep apnea
  • No metal in vivo implantation

Exclusion Criteria:

  • Diseases such as OSAS or other sleep apnea
  • Recent craniocerebral trauma (1 month)
  • Alcohol abuse and psychotropic drugs
  • EKG checking abnormality or previous history of chest tightness palpitations

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: acute intermittent hypoxia
Adjust the proportion of nitrogen and oxygen, through increasing the suction nitrogen concentration, the subject's blood oxygen saturation could decrease to 80%~90% within 30 seconds and also lasts 30 seconds; then quickly reduce the concentration of nitrogen gas suction to make the subject's blood oxygen saturation gradually return to normal level (consistent with the air inhalation), and then continue breathing air about 60 seconds to enter the next round of hypoxic state.Through adjusting the inhaled nitrogen concentration in patients, the patients could be simulated as the OSA patients who had intermittent hypoxic state due to upper airway collapse at night. This process is equivalent to acute intermittent hypoxia 25-30 times/h, which is clinically intermediate to severe OSA.
Device: acute intermittent hypoxia
Adjust the proportion of nitrogen and oxygen, through increasing the suction nitrogen concentration, the subject's blood oxygen saturation could decrease to 80%~90% within 30 seconds and also lasts 30 seconds; then quickly reduce the concentration of nitrogen gas suction to make the subject's blood oxygen saturation gradually return to normal level (consistent with the air inhalation), and then continue breathing air about 60 seconds to enter the next round of hypoxic state.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Fractional anisotropy
Time Frame: One year
Fractional anisotropy (FA) is a scalar value between zero and one that describes the degree of anisotropy of a diffusion process. A value of zero means that diffusion is isotropic, i.e. it is unrestricted (or equally restricted) in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions. FA is a measure often used in diffusion imaging where it is thought to reflect fiber density, axonal diameter, and myelination in white matter. The FA is an extension of the concept of eccentricity of conic sections in 3 dimensions, normalized to the unit range.
One year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Song Liu, M.d., Ph.D., Shanghai Jiao Tong University School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2020

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 7, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 26, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 5, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 9, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • XH-17-016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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