Intermittent Hypoxia 2: Cardiovascular and Metabolism

NCT02058823 | Terminated Phase 4

• 2 other identifiers: 2011-32P-2011-32-HI2
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare cardiovascular physiological adaptation to intermittent hypoxia (IH) of nonobese healthy subjects. The exposure will be two periods of two weeks (IH versus exposure "placebo hypoxia"). The investigators will use pharmacological tools, peripheral vasodilator (amlodipine) or specific blocker of angiotensin receptor (valsartan) versus the taking of a placebo. The allocation of the tool and the exhibition will be randomized (HI / placebo, valsartan / amlodipine). The outcome measures evaluated concern the cardiovascular system, systemic inflammation and tissular and glucose metabolism. The investigators assume an increase in arterial resistance during the intermittent hypoxia compared to the control group, these being dependent on sympathetic tone. The investigators hypothesize that the metabolic alterations that will be observed after experimental simulation (IH and fragmentation of sleep for 15 consecutive nights) will be less severe in the valsartan group than in the amlodipine group in comparison with the placebo group. A serum bank and a gene bank will be performed for the requirements of subsequent studies if necessary.

Conditions

Hypoxia; Sleep Apnea; Obstructive Sleep Apnea

Keywords

Hypoxia; Sleep apnea; Valsartan; Amlodipine; Healthy subjects; Randomized; Cross-over; International; Sympathetic nervous system

Outcome Measures

Primary Outcomes (1)

• Change in sympathetic activity

  The sympathetic activity will be directly measured by microneurography of the peroneal nerve

  Day 1 and at Day 14

Secondary Outcomes (7)

• Measure of adrenergic, inflammatory and metabolic markers in adipose tissues by chronic intermittent hypoxia versus placebo in healthy nonobese subjects.

  Day 14

• Measure variations in parameters of inflammation in adipose tissue by chronic intermittent hypoxia versus placebo in healthy nonobese subjects.

  Day 14

• Measure of metabolic aspects of the OGTT test.

  Day 14

• Measure the activation of systemic inflammation by chronic HI versus placebo in healthy nonobese subjects. The systemic inflammation will be assessed in non-stress and during the OGTT.

  Day 14

• Assessing markers implicated in the pathophysiology of chronic metabolic diseases after HI versus placebo in healthy nonobese subjects during OGTT.

  Day 14

Study Arms (4)

Arm 1: Real hypoxia and ¨Placebo

PLACEBO COMPARATOR

This arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the real hypoxia and the placebo during the first two weeks and, after the wash-out, receive the treatment of the arm 2.

Drug: Placebo

Arm 2: Hypoxia placebo and Placebo

PLACEBO COMPARATOR

This arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the hypoxia placebo and the placebo during the first two weeks and, after the wash-out, receive the treatment of the arm 1.

Drug: Placebo

Arm 3: Hypoxia and Valsartan

ACTIVE COMPARATOR

This arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the real hypoxia and the Valsartan during the first two weeks and, after the wash-out, receive the treatment of the arm 4.

Drug: Valsartan

Arm 4: Hypoxia and Amlodipine

ACTIVE COMPARATOR

This arm last 4 weeks with 2 periods of 2 weeks separated by a 6 weeks wash-out. The subjects of this arm receive the real hypoxia and the amlodipine during the first two weeks and, after the wash-out, receive the treatment of the arm 3.

Drug: Amlodipine

Interventions

Placebo DRUG

The subjects receive 1 oral pill of placebo each morning during the second week of the two periods, so 14 pills in all.

Also known as: Placebo Valsartan

Arm 1: Real hypoxia and ¨Placebo

Valsartan DRUG

The subjects receive 1 oral pill of Valsartan each morning during the second week of the two periods, so 14 pills in all. 1 pill equal 40 mg.

Also known as: Tareg

Arm 3: Hypoxia and Valsartan

Amlodipine DRUG

The subjects receive 1 oral pill of Amlodipine each morning during the second week of the two periods, so 14 pills in all. 1 pill equal 6,944 mg of amlodipine besilate with 5 mg of amlodipine.

Also known as: Effective Amlodipine

Arm 4: Hypoxia and Amlodipine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy subject
• Subject aged of 18 years-old at least
• Diagnostic AHI\<15/h and \<5% of total sleep time spent with a SaO2\<90%
• Free and informed consent signed
• Subject covered by social security
• Negative pregnancy test

You may not qualify if:

• Subject with a medical pathology (respiratory, cardiovascular, renal, metabolic, neurological...)
• Tobacco consumption \> 5 cigarettes/days
• Alcohol consumption \> 3 units/days (1 unit=1 drink)
• Subject under trusteeship or guardianship
• Subject unaffiliated with the social security
• Person deprived of their liberty, adult protected by laws, person hospitalized
• Ongoing participation in another clinical research study
• Subject non-cooperative or respectful of obligations inherent in the participation in the study

Sponsors & Collaborators

• University Hospital, Grenoble: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (1)

Laboratoire EFCR - Functional Cardio-respiratory Exploration Laboratory

La Tronche, Isère, 38700, France

Location

Related Publications (32)

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MeSH Terms

Conditions

Hypoxia; Sleep Apnea Syndromes; Sleep Apnea, Obstructive

Interventions

Valsartan; Amlodipine

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Dihydropyridines; Pyridines

Study Officials

• Renaud RT Tamisier, PhD

  University Hospital of Genoble

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2012
• First Posted: February 10, 2014
• Study Start: August 7, 2013
• Primary Completion: July 17, 2014
• Study Completion: March 16, 2017
• Last Updated: December 31, 2018

Record last verified: 2018-12

Locations

FR (1)