Impact of Estrogen + Estradiol Receptor Alpha Modulator Therapy on Oxidative Stress in Post-menopausal Women With and Without Sleep Apnea

NCT03981341 | Unknown Phase 3

• 1 other identifier: IUCPQ220519
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

One of the most likely mechanisms explaining the sleep apnea (SA)-induced increase in metabolic syndrome is the oxidative stress (OS) induced by intermittent hypoxia (IH). There are clear-cut signs of OS in postmenopausal women that may be further enhanced by SA. In rats exposed to IH, an estradiol receptor alpha agonist decreases the level of OS markers. The aims of this study are to compare OS in apneic and non-apneic postmenopausal women and to demonstrate that OS will improve after 3 months of treatment with ER alpha agonists (Duavive) in apneic post-menopausal women.

Conditions

Sleep Apnea; Post Menopausal; Oxidative Stress

Keywords

sleep apnea; post menopausal; oxidative stress

Outcome Measures

Primary Outcomes (1)

• oxidative stress

  Advanced Oxidation Protein Products

  Changes between baseline and after 3 months drug treatment

Secondary Outcomes (9)

• glucose homeostasis

  Changes between baseline and after 3 months drug treatment

• total cholesterol

  Changes between baseline and after 3 months drug treatment

• triglycerides

  Changes between baseline and after 3 months drug treatment

• aspartate aminotransferase (AST)

  Changes between baseline and after 3 months drug treatment

• gamma-glutamyl transferase (∂-GT)

  Changes between baseline and after 3 months drug treatment

Study Arms (2)

Post menopausal sleep apnea

EXPERIMENTAL

Post menopausal women with severe sleep apnea

Drug: Duavive (0.45 estrogens mg and 20 mg bazedoxifene)

Post menopausal non sleep apnea

EXPERIMENTAL

Post menopausal women without sleep apnea

Drug: Duavive (0.45 estrogens mg and 20 mg bazedoxifene)

Interventions

Duavive (0.45 estrogens mg and 20 mg bazedoxifene) DRUG

Drug given for 3 months in each participant

Post menopausal non sleep apnea; Post menopausal sleep apnea

Eligibility Criteria

• Age: 45 Years - 65 Years
• Gender Eligibility Details: post menopausal women
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• post-menopausal women
• aged 45 to 65 years
• BMI less/equal 35 kg.m-2,
• apnoea + hypopnea index (AHI) \< 15/h (non SA group) or ≥ 30/h (SA group) on a polysomnographic recording,
• % of AHI associated with obstructive events,
• regular exercise, dietary and sleep habits
• free of sleep debt (insomnia, reported habitual sleep time \> 6 h/night),
• stable medical condition.

You may not qualify if:

• clinically significant diurnal somnolence requiring immediate treatment in SA patients,
• nocturnal hypoventilation (% sleep time below 90% SaO2 \> 10 %, PaCO2 \> 45 mmHg),
• use of hormonal therapy,
• use of any medication with a respiratory depressant effect (narcotics),
• contraindication to the dug used in the protocol

Sponsors & Collaborators

• Laval University: lead
• V Joseph: collaborator
• C Minville: collaborator
• C Rheaume: collaborator

Study Sites (1)

IUCPQ

Québec, G1V 4G5, Canada

RECRUITING

Related Publications (4)

• Laouafa S, Ribon-Demars A, Marcouiller F, Roussel D, Bairam A, Pialoux V, Joseph V. Estradiol Protects Against Cardiorespiratory Dysfunctions and Oxidative Stress in Intermittent Hypoxia. Sleep. 2017 Aug 1;40(8). doi: 10.1093/sleep/zsx104.

  PMID: 28633495 BACKGROUND

• Barrera J, Chambliss KL, Ahmed M, Tanigaki K, Thompson B, McDonald JG, Mineo C, Shaul PW. Bazedoxifene and conjugated estrogen prevent diet-induced obesity, hepatic steatosis, and type 2 diabetes in mice without impacting the reproductive tract. Am J Physiol Endocrinol Metab. 2014 Aug 1;307(3):E345-54. doi: 10.1152/ajpendo.00653.2013. Epub 2014 Jun 17.

  PMID: 24939737 BACKGROUND

• Xue B, Zhao Y, Johnson AK, Hay M. Central estrogen inhibition of angiotensin II-induced hypertension in male mice and the role of reactive oxygen species. Am J Physiol Heart Circ Physiol. 2008 Sep;295(3):H1025-H1032. doi: 10.1152/ajpheart.00021.2008. Epub 2008 Jul 3.

  PMID: 18599599 BACKGROUND

• de Lima AM, Franco CM, de Castro CM, Bezerra Ade A, Ataide L Jr, Halpern A. Effects of nasal continuous positive airway pressure treatment on oxidative stress and adiponectin levels in obese patients with obstructive sleep apnea. Respiration. 2010;79(5):370-6. doi: 10.1159/000227800. Epub 2009 Jul 3.

  PMID: 19590157 BACKGROUND

MeSH Terms

Conditions

Sleep Apnea Syndromes

Interventions

bazedoxifene

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Central Study Contacts

Frederic Series

CONTACT

418 656 8711; frederic.series@med.ulaval.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director IUCPQ sleep clinic

Model Details: Open label treatment for 3 months in two parallel groups (post menopausal women without and with sleep apnea)

Study Record Dates

• First Submitted: May 22, 2019
• First Posted: June 10, 2019
• Study Start: November 1, 2019
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: April 8, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)