Flushing Reduction Associated With Nitrates

What this trial studies

A randomized, double-blinded, placebo-controlled trial of uninterrupted transdermal nitrate therapy in 140 peri- or postmenopausal women who have frequent hot flashes. Women will be randomly assigned to uninterrupted use of transdermal nitrate therapy (participant directed dose-escalation of 0.2 to 0.6 mg/hr) or identical-appearing placebo patches for 12 weeks.

Conditions in scope

• Menopausal Hot Flashes

Interventions

• transdermal nitroglycerin (Drug) — Study participants will be randomized to transdermal nitroglycerin patch or placebo patch. Participants will wear a study medication patch daily, for 12 weeks.
• Placebo (Drug) — Study participants will be randomized to transdermal nitroglycerin patch or placebo patch. Participants will wear a study medication patch daily, for 12 weeks.

Who can join

Women only · Ages 40 Years to 62 Years · Accepts healthy volunteers.

Inclusion criteria

• Women aged 40 to 62 years (consistent with the recent MSFlash hot flash network trials, and likely to maximize enrollment of highly symptomatic women)
• Postmenopausal or in the late menopausal transition. For this study, postmenopausal status will be defined by: 1) self-reported history of bilateral oophorectomy, 2) follicle stimulating hormone (FSH) levels \> 20 mU/mL for those with a self-reported history of hysterectomy without bilateral oophorectomy, or 3) no self-reported history of hysterectomy or oophorectomy, but absence of menses in the past 12 months. Late menopausal transition will be defined by amenorrhea for at least 60 days in the past 12 months within the specified age group.
• Documentation of an average of 7 or more hot flashes per 24 hours as well as 4 or more moderate-to-severe hot flashes per 24 hours as recorded on a validated 7-day screening symptom diary
• Willing to refrain from initiating other treatments that are known to affect the frequency of severity hot flashes during the trial period
• Report having a current primary health care provider (such as a general practitioner, family medicine, internal medicine, or nurse practitioner providing primary care or specializing in women's health)

Exclusion criteria

• Current or recent use of NTG or other nitrate-containing medications (i.e., use within 1 month of screening), or intention to use nitrate-containing medication during the interventional period
• Current or recent use of medications already known to reduce the frequency or severity of hot flashes (e.g., vaginal or transdermal estrogens in the past 4 weeks; oral estrogens or progestins in the past 8 weeks; intrauterine progestin therapy in the past 8 weeks; progestin implants or estrogen alone injectable therapy in the past 3 months; estrogen pellet therapy or progestin injectable therapy in the past 6 months; clonidine, methyldopa, gabapentin, pregabalin and selective serotonin or norepinephrine reuptake inhibitors (SSRIs/SNRIs) in the past 1 month); or intention to use these medications during the interventional period
• Current or recent use of phosphodiesterase inhibitor medications (within 1 month of screening), or intention to use these medications during the interventional period
• Current or recent use of riociguat, a soluble guanylate cyclase stimulator medication, within 1 month of screening, or intention to use riociguat during the interventional period
• Self-reported history of hypertrophic obstructive cardiomyopathy, aortic valve stenosis, or mitral valve stenosis (since symptoms of these conditions may be aggravated by NTG therapy)
• Self-reported history of coronary disease (since patients with coronary disease may need NTG therapy for chest pain or may be at increased risk of new coronary events in the setting of nitrate tolerance), or evidence of prior myocardial infarction on screening electrocardiogram (ECG)
• Self-reported history of diabetes or 2 or more major risk factors for coronary disease (i.e., smoking, hypertension, or hyperlipidemia with physician-recommended pharmacologic treatment)
• Evidence of tachyarrhythmias such as atrial fibrillation or flutter without adequate rate control (\>110 beats/minute) on screening ECG

Eligibility wording paraphrased from the public record. View the full criteria on ClinicalTrials.gov before contacting a site.

Where it’s happening

Status & timeline

• Overall status: Completed
• Study type: Interventional
• Phase: PHASE2
• Start date: 2017-04-24
• Primary completion: 2022-03-08
• Last update posted: 2025-03-28
• First posted: 2016-03-21

Sponsor & contact

Lead sponsor: Alison Huang, MD (Other)

Collaborators: National Institute on Aging (NIA)

For trial site contact information, use the official record at ClinicalTrials.gov. Contact details change frequently and the public record is the source of truth.

Outcome measures

Primary outcomes

• Change From Baseline Hot Flash Frequency (Repeated change from baseline to 5 and 12 weeks)
  Change was calculated as the followup value minus the baseline value. Values are model generated Least Square Means for combined 5 and 12 month time points.

Related ClearedRx care

If you’re reading this trial because you have menopause symptoms now, you don’t have to wait for a trial to access evidence-based care. ClearedRx prescribes the same FDA-approved and compounded HRT products that have been studied in trials like this one for decades.