Flushing Reduction Associated With Nitrates

NCT02714205 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 15-184725R01AG050588-04
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Menopausal Hot Flashes

Keywords

Hot flash

Outcome Measures

Primary Outcomes (1)

• Change From Baseline Hot Flash Frequency

  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.

  Repeated change from baseline to 5 and 12 weeks

Secondary Outcomes (7)

• Change From Baseline Hot Flash Related Daily Interference Scale (HFRDIS) Score

  Repeated change from baseline to 5 and 12 weeks

• Change From Baseline Menopause Quality of Life (MENQOL), Vasomotor Domain Score

  Repeated change from baseline to 5 and 12 weeks

• Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score

  Repeated change from baseline to 5 and 12 weeks

• Change From Baseline Generalized Anxiety Disorder-7 (GAD-7) Score

  Repeated change from baseline to 5 and 12 weeks

• Change From Baseline Center for Epidemiologic Studies Depression (CES-D) Score

  Repeated change from baseline to 5 and 12 weeks

Other Outcomes (1)

• Number of Participants With Treatment Related Severe Adverse Events Defined by Common Terminology Criteria for Adverse Events (CTCAE) Severity Grade 3 or Higher.

  Baseline to 12 weeks

Study Arms (2)

Transdermal Nitroglycerin

EXPERIMENTAL

Daily transdermal nitroglycerin patch, starting at 0.2 mg/hr. Dose escalation up to 0.6 mg/hr.

Drug: transdermal nitroglycerin

Placebo

PLACEBO COMPARATOR

Daily transdermal placebo patch.

Drug: Placebo

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.

Transdermal Nitroglycerin

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.

Placebo

Eligibility Criteria

• Age: 40 Years - 62 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Alison Huang, MD: lead
• National Institute on Aging (NIA): collaborator

Study Sites (2)

University of California, San Francisco

Oakland, California, 94612, United States

Location

University of California, San Francisco

San Francisco, California, 94115, United States

Location

Related Publications (1)

• Huang AJ, Cummings SR, Ganz P, Schembri M, Raghunathan H, Vittinghoff E, Gibson CJ, Grady D. Efficacy of Continuous Transdermal Nitroglycerin for Treating Hot Flashes by Inducing Nitrate Cross-tolerance in Perimenopausal and Postmenopausal Women: A Randomized Clinical Trial. JAMA Intern Med. 2023 Aug 1;183(8):776-783. doi: 10.1001/jamainternmed.2023.1977.

  PMID: 37273224 DERIVED

MeSH Terms

Conditions

Hot Flashes

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Mike Schembri, Data Systems Analyst
• Organization: University of California, San Francisco

michael.schembri@ucsf.edu

415-353-7161

Study Officials

• Alison Huang, MD, MPhil, MAS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: March 11, 2016
• First Posted: March 21, 2016
• Study Start: April 24, 2017
• Primary Completion: March 8, 2022
• Study Completion: April 5, 2022
• Last Updated: March 28, 2025
• Results First Posted: May 18, 2023

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)