Hot Flash as a Marker of Cardiovascular Risk in Recent Postmenopause: Effects of Non-hormonal Treatments

NCT03149419 | Completed Phase 4

• 1 other identifier: CAAE 6717515.1.0000.5259
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

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.

Conditions

Postmenopausal Flushing; Cardiovascular Risk Factor; Endothelial Dysfunction

Keywords

postmenopause; paroxetine; endothelial dysfunction; blood pressure; heart rate variability; sleep quality; perceived stress; sleepiness

Outcome Measures

Primary Outcomes (1)

• Endothelial function in non invasive venous occlusion plethysmography

  Forearm blood flow (ml/min per 100 ml)

  12 weeks

Study Arms (2)

Paroxetine

ACTIVE COMPARATOR

Paroxetine 7,5 mg - 1 pill/day for 12 weeks

Drug: Paroxetine

Placebo

PLACEBO COMPARATOR

Placebo oral capsule (corn starch) - 1 pill/day for 12 weeks

Drug: Placebo oral capsule

Interventions

Paroxetine DRUG

Paroxetine

Placebo oral capsule DRUG

Placebo

Eligibility Criteria

• Age: 45 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• \> 10 years of hypoestrogenism
• Smoking
• Diabetes mellitus or altered fasting glycemia in use of oral hypoglycemic agents or insulin
• BMI ≥ 35 Kg / m2
• Uncontrolled hypertension - blood pressure (BP) ≥ 140/90 mmHg
• 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;
• Uncompensated hypo or hyperthyroidism;
• Previous cardiovascular event history.

Sponsors & Collaborators

• Rio de Janeiro State University: lead

Study Sites (1)

Universidade do Estado do Rio de Janeiro

Rio de Janeiro, 20550-900, Brazil

Location

Related Publications (5)

• Taddei S, Virdis A, Ghiadoni L, Mattei P, Sudano I, Bernini G, Pinto S, Salvetti A. Menopause is associated with endothelial dysfunction in women. Hypertension. 1996 Oct;28(4):576-82. doi: 10.1161/01.hyp.28.4.576.

  PMID: 8843881 BACKGROUND

• 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.

  PMID: 20080857 BACKGROUND

• 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.

  PMID: 22132748 BACKGROUND

• 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.

  PMID: 27219834 BACKGROUND

• 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.

  PMID: 24806158 BACKGROUND

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders; Sleepiness

Interventions

Paroxetine

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ciciliana MZ Rech

  Universidade do Estado do Rio de Janeiro- BioVasc laboratory

  PRINCIPAL INVESTIGATOR

• Ruth Clapauch, PhD

  Rio de Janeiro State University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 18, 2017
• First Posted: May 11, 2017
• Study Start: March 1, 2016
• Primary Completion: September 30, 2017
• Study Completion: March 30, 2018
• Last Updated: April 12, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)