Clinical trial NCT03149419: Hot Flash as a Marker of Cardiovascular Risk in Recent Postmenopause: Effects of Non-hormonal Treatments
Official title: Endothelial, Autonomic and Pressure Effects of Paroxetine in Recent Postmenopause Women With Hot Flashes: a Randomized Placebo Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Postmenopausal Flushing
Cardiovascular Risk Factor
Endothelial Dysfunction
Keywords: postmenopause
paroxetine
endothelial dysfunction
blood pressure
heart rate variability
sleep quality
perceived stress
sleepiness
Lead sponsor: Rio de Janeiro State University
Sponsor class: OTHER
First posted: 2017-05-11
Enrollment: 140
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hot flashes, vasomotor symptoms that affect many postmenopausal women, are associated with cardiovascular disease and endothelial dysfunction. Estrogen therapy, associated or not with progestogens, is the standard treatment for vasomotor symptoms and improves the endothelial function of postmenopausal women with hot flushes, even those with cardiovascular risk factors, such as hypertension. It is not known whether hot flushes are a cause for the development of endothelial dysfunction or are markers of this dysfunction, evidenced by estrogen deficiency, thus representing primitive target organ (vessel) lesion. Paroxetine was approved by the FDA as a non hormonal treatment for menopausal hot flashes. In this double-blind randomized clinical trial, the vascular effects of paroxetine at a dose of 7.5 mg / day, compared to placebo, during 12 weeks are evaluated.

Detailed description: Paroxetine and placebo effects at baseline and after 12 weeks in endothelial, autonomic and pressure components of vascular function are evaluated.

Non invasive venous occlusion plethysmography is used to study endothelial function; ambulatory blood pressure monitoring is used to study blood pressure variations during daytime and nocturnal descent; autonomic function is studied following sympathetic and parasympathetic parameters through heart rate variability.

The effects of paroxetine and placebo are also evaluated on:

* daytime sleepiness (through Epworth Sleepiness Scale ),
* sleep quality (through Pittsburgh Sleep Quality Index),
* perceived stress (through Perceived Scale Stress).

Biochemical and hormonal profiles including complete lipid profile, fasting glucose, insulin, estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH); inflammatory and oxidative stress markers are also studied.

Eligibility criteria: Inclusion Criteria:

1. Postmenopause
2. Present hot flushes (note ≥ 3 on a scale of 0 to 10)

Exclusion Criteria:

1. \> 10 years of hypoestrogenism
2. Smoking
3. Diabetes mellitus or altered fasting glycemia in use of oral hypoglycemic agents or insulin
4. BMI ≥ 35 Kg / m2
5. Uncontrolled hypertension - blood pressure (BP) ≥ 140/90 mmHg
6. Users of glucocorticoids, phytoestrogens, β-blockers, selective serotonin reuptake inhibitors (SSRIs), selective noradrenaline reuptake inhibitors (SNRIs), clonidine, gabapentin, pregabalin, cinnarizine, alphamethyldopa or any drugs with effects on the central nervous system;
7. Uncompensated hypo or hyperthyroidism;
8. Previous cardiovascular event history.

Primary outcomes:
measure: Endothelial function in non invasive venous occlusion plethysmography
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: Universidade do Estado do Rio de Janeiro
Study officials:
affiliation: Universidade do Estado do Rio de Janeiro- BioVasc laboratory
name: Ciciliana MZ Rech
role: PRINCIPAL_INVESTIGATOR
affiliation: Rio de Janeiro State University
name: Ruth Clapauch, PhD
role: STUDY_CHAIR
References:
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citation: Bechlioulis A, Kalantaridou SN, Naka KK, Chatzikyriakidou A, Calis KA, Makrigiannakis A, Papanikolaou O, Kaponis A, Katsouras C, Georgiou I, Chrousos GP, Michalis LK. Endothelial function, but not carotid intima-media thickness, is affected early in menopause and is associated with severity of hot flushes. J Clin Endocrinol Metab. 2010 Mar;95(3):1199-206. doi: 10.1210/jc.2009-2262. Epub 2010 Jan 15.
citation: Lambrinoudaki I, Augoulea A, Armeni E, Rizos D, Alexandrou A, Creatsa M, Kazani M, Georgiopoulos G, Livada A, Exarchakou A, Stamatelopoulos K. Menopausal symptoms are associated with subclinical atherosclerosis in healthy recently postmenopausal women. Climacteric. 2012 Aug;15(4):350-7. doi: 10.3109/13697137.2011.618564. Epub 2011 Dec 1.
citation: Silveira JS, Clapauch R, Souza Md, Bouskela E. Hot flashes: emerging cardiovascular risk factors in recent and late postmenopause and their association with higher blood pressure. Menopause. 2016 Aug;23(8):846-55. doi: 10.1097/GME.0000000000000641.
citation: Orleans RJ, Li L, Kim MJ, Guo J, Sobhan M, Soule L, Joffe HV. FDA approval of paroxetine for menopausal hot flushes. N Engl J Med. 2014 May 8;370(19):1777-9. doi: 10.1056/NEJMp1402080. No abstract available.