Flushing Reduction Associated With Nitrates
Condition: Menopausal Hot Flashes
MeSH terms: Hot Flashes; Flushing
Intervention: transdermal nitroglycerin; Placebo
Intervention description: Study participants will be randomized to transdermal nitroglycerin patch or placebo patch. Participants will wear a study medication patch daily, for 12 weeks.; Study participants will be randomized to transdermal nitroglycerin patch or placebo patch. Participants will wear a study medication patch daily, for 12 weeks.
Intervention MeSH terms: Nitroglycerin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 141.0
Sex: Female
Minimum age: 40 Years
Maximum age: 62 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Hot flash

Summary:

      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.
    

Eligibility criteria:

        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

          -  Evidence of second or third-degree atrioventricular block on screening ECG

          -  Hypotension based on measured resting blood pressure <90/60 at baseline; or normal
             resting blood pressure but evidence of orthostatic hypotension with change from supine
             to standing position)

          -  Uncontrolled hypertension based on measured resting blood pressure > 180/110 at
             baseline

          -  Self-reported headaches interfering with activities of daily activities more than
             twice a month, or use of prescription medication to prevent or treat headache in the
             past month (since these may be worsened by NTG therapy)

          -  Known allergy to nitroglycerin or other nitrate-based medications.

          -  Known skin sensitivity to adhesives (which may generalize to the NTG patches)

          -  Unable to complete or tolerate a brief 3-day run-in period involving the lowest
             available dose of NTG (0.1 mg/hr)

          -  Currently pregnant, gave birth within the past 3 months, planning pregnancy during the
             study period, or unwilling to use regular barrier contraception or abstain from sexual
             activity to prevent pregnancy if not yet postmenopausal

          -  Currently breastfeeding, breastfeeding within the past 3 months, or planning to
             breastfeed during the study period

          -  Self-report heavy alcohol use (>3 drinks in a given day or >7 drinks per week) and
             uncomfortable or unwilling to decrease their alcohol intake during the study period.

          -  Unable or unwilling to provide informed consent, fill out questionnaires, or complete
             study visits in English

          -  Report other conditions that, in the judgment of the investigators, render potential
             participants highly unlikely to follow the protocol, including plans to move,
             substance abuse, significant psychiatric problems, or severe dementia.