Menopausal Hot FlashesPhase 2FRANNCT02714205
Flushing Reduction Associated With Nitrates
A Phase 2 study testing transdermal nitroglycerin in people with Menopausal Hot Flashes, run by Alison Huang, MD at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 62 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Menopausal Hot Flashes
- What is being tested?
- transdermal nitroglycerin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 141 participants
- Where
- 2 sitesUnited States
- Study dates
- 24 Apr 2017to 5 Apr 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 62 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
Who cannot join
- 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)
Show all 20Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of California, San Francisco
Oakland, California, 94612
University of California, San Francisco
San Francisco, California, 94115
About this study
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
- Being tested
- transdermal nitroglycerin, Placebo
- Keywords
- Hot flash
- Medical subject headings
- Hot Flashes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transdermal nitroglycerinDrug
Study participants will be randomized to transdermal nitroglycerin patch or placebo patch. Participants will wear a study medication patch daily, for 12 weeks.
PlaceboDrug
Study participants will be randomized to transdermal nitroglycerin patch or placebo patch. Participants will wear a study medication patch daily, for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Transdermal Nitroglycerin | Experimental | Daily transdermal nitroglycerin patch, starting at 0.2 mg/hr. Dose escalation up to 0.6 mg/hr. Receives: Drug: transdermal nitroglycerin |
| Placebo | Placebo comparator | Daily transdermal placebo patch. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Repeated change from baseline to 5 and 12 weeks
Secondary outcomes (7)
Change From Baseline Hot Flash Related Daily Interference Scale (HFRDIS) Score
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.
Range 0-100, Higher score indicates lower quality of life
Measured: Repeated change from baseline to 5 and 12 weeks
Change From Baseline Menopause Quality of Life (MENQOL), Vasomotor Domain Score
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.
Range 1-8, Higher score indicates lower quality of life
Measured: Repeated change from baseline to 5 and 12 weeks
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score
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 Range 0-21, Higher score indicates lower quality of life
Measured: Repeated change from baseline to 5 and 12 weeks
Change From Baseline Generalized Anxiety Disorder-7 (GAD-7) Score
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 Range 0-21, Higher score indicates lower quality of life
Measured: Repeated change from baseline to 5 and 12 weeks
Change From Baseline Center for Epidemiologic Studies Depression (CES-D) Score
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 Range 0-60, a higher score indicates a lower quality of life.
Measured: Repeated change from baseline to 5 and 12 weeks
Change in Baseline Frequency of Moderate-to-severe Hot Flashes
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
Measured: Repeated change from baseline to 5 and 12 weeks
Change in Baseline Total Hot Flash Severity Score
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. The hot flash severity score is calculated as the sum of severity ratings for all hot flashes recorded on the symptom over a 7-day period (mild=1, moderate=2, severe=3), and then divided by 7 for the daily average score.
Range 12-60, higher score indicates lower quality of life.
Measured: Repeated change from baseline to 5 and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2016 (estimated)
- Study start24 Apr 2017
- Primary completion8 Mar 2022
- Study completion5 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Menopausal Hot FlashesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 141 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alison Huang, MD
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor-investigator, Alison Huang, MD, University of California, San Francisco
- Investigators
- Alison Huang, MD, MPhil, MAS, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02714205
- Sponsor's protocol ID
- 15-18472
- Other IDs
- 5R01AG050588-04
- Acronym
- FRAN
- Status last verified
- Mar 2025
- First submitted
- 11 Mar 2016
- Last updated
- 28 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37273224
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Flushing Reduction Associated With Nitrates
- ClinicalTrials.gov ID
- NCT02714205
- Acronym / sponsor ID
- FRAN / 15-18472
- Conditions
- Menopausal Hot Flashes
- Keywords
- Hot flash
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 141 participants (actual)
- Lead sponsor
- Alison Huang, MDUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 24 Apr 2017 (actual)
- Primary completion
- 8 Mar 2022 (actual)
- Study completion
- 5 Apr 2022 (actual)
- First posted
- 21 Mar 2016 (estimated)
- Results
- Posted 18 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Transdermal Nitroglycerin | Experimental | Drug: transdermal nitroglycerinDaily transdermal nitroglycerin patch, starting at 0.2 mg/hr. Dose escalation up to 0.6 mg/hr. |
| Placebo | Placebo comparator | Drug: PlaceboDaily transdermal placebo patch. |
Who may qualify
- Ages
- 40 to 62 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (20 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| transdermal nitroglycerinStudy participants will be randomized to transdermal nitroglycerin patch or placebo patch. Participants will wear a study medication patch daily, for 12 weeks. | Drug | Transdermal Nitroglycerin |
| PlaceboStudy participants will be randomized to transdermal nitroglycerin patch or placebo patch. Participants will wear a study medication patch daily, for 12 weeks. | Drug | Placebo |
Primary outcome
Change From Baseline Hot Flash Frequency
Time frame: 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.
7 secondary outcomes
Change From Baseline Hot Flash Related Daily Interference Scale (HFRDIS) Score
Time frame: Repeated change from baseline to 5 and 12 weeks
Change From Baseline Menopause Quality of Life (MENQOL), Vasomotor Domain Score
Time frame: Repeated change from baseline to 5 and 12 weeks
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score
Time frame: Repeated change from baseline to 5 and 12 weeks
Change From Baseline Generalized Anxiety Disorder-7 (GAD-7) Score
Time frame: Repeated change from baseline to 5 and 12 weeks
Change From Baseline Center for Epidemiologic Studies Depression (CES-D) Score
Time frame: Repeated change from baseline to 5 and 12 weeks
Change in Baseline Frequency of Moderate-to-severe Hot Flashes
Time frame: Repeated change from baseline to 5 and 12 weeks
Change in Baseline Total Hot Flash Severity Score
Time frame: Repeated change from baseline to 5 and 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37273224Huang 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.
- Individual participant dataSharing planned: No
Related trials for Menopausal Hot Flashes
Not yet recruiting
Internet-Delivered CBT Program for Menopausal Vasomotor Symptoms
Menopause, Menopausal Vasomotor Symptoms
Not yet recruiting
Self-Management Box on Hot Flash in Postmenopausal Women
Postmenopausal Flushing, Postmenopausal Symptoms
Recruiting
Effects of a Dietary Supplement in Women With Late Perimenopause or Early Postmenopause
Perimenopause, Postmenopause
RecruitingPhase 2
Safety and Efficacy of Asimadoline (TP0052) in Patients With Vasomotor Symptoms (VMS).
Vasomotor Symptoms
RecruitingPhase 4
The Effect of Tirzepatide on Menopausal Vasomotor Symptoms and Biological Aging in Post-menopausal Women With Obesity
Obesity, Menopause Hot Flashes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alison Huang, MD, MPhil, MAS principal investigator
University of California, San Francisco
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing transdermal nitroglycerin in people with Menopausal Hot Flashes, run by Alison Huang, MD at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline Hot Flash Frequency (time frame: Repeated change from baseline to 5 and 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02714205, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2025.