FlushingEarly Phase 1NCT03497442
Treatment of Asian Flushing Syndrome With Topical Alpha Agonists
A Early Phase 1 study testing Brimonidine Tartrate in people with Flushing and Alcohol-Related Disorders, run by University of California, San Francisco at 1 site in United States.
Trial summary
Asian Flushing Syndrome (AFS) is a genetic disease affecting approximately 70% of patients of East Asian descent characterized by severe flushing with minimal ethanol consumption. This reaction is cosmetically unattractive and socially limiting. Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Flushing, Alcohol-Related Disorders, Aldehyde Dehydrogenase Deficiency
- What is being tested?
- Brimonidine Tartrate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jul 2018to 25 Mar 2019
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female, 21 years of age or older
- Self-reported East Asian descent defined as being at least partially ethnically Han Chinese, Japanese, or Korean.
- No persistent facial erythema at baseline as reported by the patient and observed by investigators at first visit
- Moderate to severe facial erythema (grade of 2 or more on the Clinician Erythema Assessment scale) induced by one standard drink of alcohol as defined by the National Institute on Alcohol Abuse and Alcoholism (12 ounces of beer, 5% alcohol; 5 ounces of wine, 12% alcohol; or 1.5 ounces of distilled spirits, 40% alcohol). Patients must provide a photo of themselves in sufficient lighting after having one standard drink to be confirmed by the investigators at the screening visit.
- Written informed consent for any and all study procedures
- Written authorization for use and release of health and research study information
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- Written authorization for use of photos in publications and presentations
- Ability to follow study instructions and complete study assessment tools without assistance.
- Ability to communicate with the study team without the need for translators.
- Female patients of childbearing potential must have a negative urine pregnancy test result at the screening visit.
Who cannot join
- Age < 21
- Known hypersensitivity or allergies to any component of the study treatment
- Pregnancy or active breastfeeding
- History of rosacea
- Exam findings consistent with rosacea
- Current use of medications for rosacea
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- Current use of oral H1 or H2 antagonists, or use in the last 2 weeks
- Active acne vulgaris
- Current use of topical medications for acne vulgaris
- Any uncontrolled systemic disease or abnormal vital signs at study visit
- Current use of medications known to cause cutaneous flushing such as rifampin, nicotinic acid, calcium channel blockers (or other antihypertensives), nitroglycerin, prostaglandins, bromocriptine, tamoxifen, thyroid hormone replacement, cyproterone acetate (or other medications to induce fertility), sildenafil citrate, and monoamine oxidase inhibitors
- Current use of medications known to be contraindicated with alcohol use such as disulfiram, rifampin, isoniazid, isotretinoin, anxiolytics, non-steroidal anti-inflammatory medications, acetaminophen, warfarin, antidepressants, St. John's Wort, cyclobenzaprine and other muscle relaxants, metronidazole, trimethoprim-sulfamethoxazole.
- History of any of the following conditions: Raynaud's syndrome, orthostatic hypotension, cerebral or coronary insufficiency, congenital or acquired heart disease, thromboangiitis obliterans, alcohol or substance abuse, liver fibrosis or cirrhosis, hepatitis, renal insufficiency, severe gastrointestinal bleeding, seizures, or psychiatric disease.
- Protected or vulnerable patient groups such as inmates, children and minors, pregnant women, and individuals with cognitive impairment or those who are legally blind, illiterate, or cannot talk or write.
- Use of any products containing oxymetazoline or brimonidine within 2 weeks of initial study visit.
- Use of topical glucocorticosteroids applied to the face within 2 weeks of initial study visit
- Any prior treatment with lasers, intense pulsed light, photodynamic therapy, or other energy based therapy to the face.
- Facial hair, tattoos, facial characteristics, or cutaneous disease (such as actinic damage, melasma, postinflammatory hyper- or hypopigmentation, excessive telangiectasias, nevi, or other pigmentation) which may interfere with assessments of erythema in the opinion of the investigators.
- Current enrollment in an investigational drug or device study or participation in such within 30 days of entry into this study.
- Any condition or situation that, in the investigator's opinion, may put the patient at significant risk, or may significantly interfere with the patient's participation in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Asian Flushing Syndrome (AFS) is a genetic disease affecting approximately 70% of patients of East Asian descent characterized by severe flushing with minimal ethanol consumption. This reaction is cosmetically unattractive and socially limiting. Many Asian patients avoid drinking alcohol on dates, at weddings, and during business events because of this reaction and the perception of being drunk or alcoholic.
Ethanol is normally metabolized to acetic acid by two enzymes. The first enzyme, alcohol dehydrogenase (ADH) converts ethanol to acetaldehyde. The second enzyme, aldehyde dehydrogenase 2 (ALDH2) converts the toxic acetaldehyde to harmless acetic acid. When ADH function is increased or ALDH2 function is decreased, the toxic intermediate acetaldehyde accumulates resulting in cutaneous flushing. Over 70% of East Asians have genetic polymorphisms in either ADH or ALDH2 leading to intense flushing with ethanol consumption.
Read more
There are no effective topical treatments for the Asian Flushing Syndrome. Oral antihistamines have been used with some success in treating symptoms of Asian Flushing Syndrome; however these can have sedating effects and may be dangerous in combination with alcohol.
Brimonidine is a selective α2-adrenoceptor agonist that acts through vasoconstriction and is commercially available in a topical gel. This topical treatment is FDA approved for the indication of facial flushing and has a long history of safety in human subjects.
- Being tested
- Brimonidine Tartrate, Placebo Vehicle Gel
- Medical subject headings
- Flushing, Alcohol-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brimonidine TartrateDrug
Also called Mirvaso
Topical brimonidine tartrate will be applied to one half of each participant's face. A randomization process will be used to determine which side of the face each participant will apply treatment to. The untreated side of the face will receive a placebo vehicle. Patient and clinician will be blinded to treatment side.
Placebo Vehicle GelDrug
Vehicle Gel
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | This is a randomized vehicle controlled, double blinded, interventional study. Patients of East Asian descent with a history of Asian Flushing Syndrome will be asked to apply a thin layer of brimonidine 0.33% gel to one half of their face thirty minutes before consuming alcohol (1.5 oz vodka for women, 3.0 oz vodka for men). The Photos will be taken 30 minutes, one hour, and 1.5 hours after consumption of alcohol. Erythema will be assessed at each time point by both the patient and study investigator using a 5- point erythema assesment score. Patient blood alcohol content (BAC) will be measured noninvasively at each time point. Receives: Drug: Brimonidine Tartrate |
| Placebo Arm | Placebo comparator | This is a randomized vehicle controlled, double blinded, interventional study. Patients of East Asian descent with a history of Asian Flushing Syndrome will be asked to apply a thin layer of vehicle gel to one half of their face thirty minutes before consuming alcohol (1.5 oz vodka for women, 3.0 oz vodka for men). The Photos will be taken 30 minutes, one hour, and 1.5 hours after consumption of alcohol. Erythema will be assessed at each time point by both the patient and study investigator using a 5- point erythema assesment score. Patient blood alcohol content (BAC) will be measured noninvasively at each time point. Receives: Drug: Placebo Vehicle Gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinician Erythema Score
Clinician Erythema Assessment (CEA) Scale Grade 0: Clear skin with no signs of erythema Grade 1: Almost clear of erythema, slight redness Grade 2: Mild erythema, definite redness Grade 3: Moderate erythema, marked redness Grade 4: Severe erythema, fiery redness.
Measured: Evaluated 30 minutes after alcohol consumption
Patient Erythema Self Assessment
Subject self-assessment 0: No signs of unwanted redness
- Almost clear of unwanted redness
- Mild redness
- Moderate redness
- Severe redness
Measured: Evaluated 30 minutes after alcohol consumption
Secondary outcomes (2)
Delayed Clinician Erythema Score
Clinician Erythema Assessment (CEA) Scale
Measured: Evaluated 60 and 90 minutes after alcohol consumption
Delayed Patient Erythema Self Assessment
Subject self-assessment
Measured: Evaluated 60 and 90 minutes after alcohol consumption
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2018
- Study start12 Jul 2018
- Primary completion25 Mar 2019
- Study completion25 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for FlushingStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wesley Yu, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03497442
- Sponsor's protocol ID
- 17-23964
- Status last verified
- Apr 2020
- First submitted
- 5 Apr 2018
- Last updated
- 4 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Brooks PJ, Enoch MA, Goldman D, Li TK, Yokoyama A. The alcohol flushing response: an unrecognized risk factor for esophageal cancer from alcohol consumption. PLoS Med. 2009 Mar 24;6(3):e50. doi: 10.1371/journal.pmed.1000050.
PubMed 19320537Eng MY, Luczak SE, Wall TL. ALDH2, ADH1B, and ADH1C genotypes in Asians: a literature review. Alcohol Res Health. 2007;30(1):22-7.
PubMed 17718397Miller NS, Goodwin DW, Jones FC, Gabrielli WF, Pardo MP, Anand MM, Hall TB. Antihistamine blockade of alcohol-induced flushing in orientals. J Stud Alcohol. 1988 Jan;49(1):16-20. doi: 10.15288/jsa.1988.49.16.
PubMed 3347071Altura BM, Carella A, Altura BT. Acetaldehyde on vascular smooth muscle: possible role in vasodilator action of ethanol. Eur J Pharmacol. 1978 Nov 1;52(1):73-83. doi: 10.1016/0014-2999(78)90023-7.
PubMed 720389Yu WY, Lu B, Tan D, Aroyan C, Shinkai K, Leslie KS, Fox LP, Yu S, Neuhaus IM, Grekin RC, Arron ST. Effect of Topical Brimonidine on Alcohol-Induced Flushing in Asian Individuals: A Randomized Clinical Trial. JAMA Dermatol. 2020 Feb 1;156(2):182-185. doi: 10.1001/jamadermatol.2019.3508.
PubMed 31799996
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Asian Flushing Syndrome With Topical Alpha Agonists
- ClinicalTrials.gov ID
- NCT03497442
- Acronym / sponsor ID
- 17-23964
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- 12 Jul 2018 (actual)
- Primary completion
- 25 Mar 2019 (actual)
- Study completion
- 25 Mar 2019 (actual)
- First posted
- 13 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Asian Flushing Syndrome (AFS) is a genetic disease affecting approximately 70% of patients of East Asian descent characterized by severe flushing with minimal ethanol consumption. This reaction is cosmetically unattractive and socially limiting. Many Asian patients avoid drinking alcohol on dates, at weddings, and during business events because of this reaction and the perception of being drunk or alcoholic.
Ethanol is normally metabolized to acetic acid by two enzymes. The first enzyme, alcohol dehydrogenase (ADH) converts ethanol to acetaldehyde. The second enzyme, aldehyde dehydrogenase 2 (ALDH2) converts the toxic acetaldehyde to harmless acetic acid. When ADH function is increased or ALDH2 function is decreased, the toxic intermediate acetaldehyde accumulates resulting in cutaneous flushing. Over 70% of East Asians have genetic polymorphisms in either ADH or ALDH2 leading to intense flushing with ethanol consumption.
There are no effective topical treatments for the Asian Flushing Syndrome. Oral antihistamines have been used with some success in treating symptoms of Asian Flushing Syndrome; however these can have sedating effects and may be dangerous in combination with alcohol.
Brimonidine is a selective α2-adrenoceptor agonist that acts through vasoconstriction and is commercially available in a topical gel. This topical treatment is FDA approved for the indication of facial flushing and has a long history of safety in human subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: Brimonidine TartrateThis is a randomized vehicle controlled, double blinded, interventional study. Patients of East Asian descent with a history of Asian Flushing Syndrome will be asked to apply a thin layer of brimonidine 0.33% gel to one half of their face thirty minutes before consuming alcohol (1.5 oz vodka for women, 3.0 oz vodka for men). The Photos will be taken 30 minutes, one hour, and 1.5 hours after consumption of alcohol. Erythema will be assessed at each time point by both the patient and study investigator using a 5- point erythema assesment score. Patient blood alcohol content (BAC) will be measured noninvasively at each time point. |
| Placebo Arm | Placebo comparator | Drug: Placebo Vehicle GelThis is a randomized vehicle controlled, double blinded, interventional study. Patients of East Asian descent with a history of Asian Flushing Syndrome will be asked to apply a thin layer of vehicle gel to one half of their face thirty minutes before consuming alcohol (1.5 oz vodka for women, 3.0 oz vodka for men). The Photos will be taken 30 minutes, one hour, and 1.5 hours after consumption of alcohol. Erythema will be assessed at each time point by both the patient and study investigator using a 5- point erythema assesment score. Patient blood alcohol content (BAC) will be measured noninvasively at each time point. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female, 21 years of age or older
- Self-reported East Asian descent defined as being at least partially ethnically Han Chinese, Japanese, or Korean.
- No persistent facial erythema at baseline as reported by the patient and observed by investigators at first visit
- Moderate to severe facial erythema (grade of 2 or more on the Clinician Erythema Assessment scale) induced by one standard drink of alcohol as defined by the National Institute on Alcohol Abuse and Alcoholism (12 ounces of beer, 5% alcohol; 5 ounces of wine, 12% alcohol; or 1.5 ounces of distilled spirits, 40% alcohol). Patients must provide a photo of themselves in sufficient lighting after having one standard drink to be confirmed by the investigators at the screening visit.
- Written informed consent for any and all study procedures
Key exclusion criteria (20 listed)
- Age < 21
- Known hypersensitivity or allergies to any component of the study treatment
- Pregnancy or active breastfeeding
- History of rosacea
- Exam findings consistent with rosacea
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 |
|---|---|---|
| Brimonidine TartrateAlso: MirvasoTopical brimonidine tartrate will be applied to one half of each participant's face. A randomization process will be used to determine which side of the face each participant will apply treatment to. The untreated side of the face will receive a placebo vehicle. Patient and clinician will be blinded to treatment side. | Drug | Treatment Arm |
| Placebo Vehicle GelVehicle Gel | Drug | Placebo Arm |
Primary outcome
Clinician Erythema Score
Time frame: Evaluated 30 minutes after alcohol consumption
Clinician Erythema Assessment (CEA) Scale Grade 0: Clear skin with no signs of erythema Grade 1: Almost clear of erythema, slight redness Grade 2: Mild erythema, definite redness Grade 3: Moderate erythema, marked redness Grade 4: Severe erythema, fiery redness.
Patient Erythema Self Assessment
Time frame: Evaluated 30 minutes after alcohol consumption
Subject self-assessment 0: No signs of unwanted redness 1. Almost clear of unwanted redness 2. Mild redness 3. Moderate redness 4. Severe redness
2 secondary outcomes
Delayed Clinician Erythema Score
Time frame: Evaluated 60 and 90 minutes after alcohol consumption
Delayed Patient Erythema Self Assessment
Time frame: Evaluated 60 and 90 minutes after alcohol consumption
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2020.
- Background: PubMed 19320537Brooks PJ, Enoch MA, Goldman D, Li TK, Yokoyama A. The alcohol flushing response: an unrecognized risk factor for esophageal cancer from alcohol consumption. PLoS Med. 2009 Mar 24;6(3):e50. doi: 10.1371/journal.pmed.1000050.
- Background: PubMed 17718397Eng MY, Luczak SE, Wall TL. ALDH2, ADH1B, and ADH1C genotypes in Asians: a literature review. Alcohol Res Health. 2007;30(1):22-7.
- Background: PubMed 3347071Miller NS, Goodwin DW, Jones FC, Gabrielli WF, Pardo MP, Anand MM, Hall TB. Antihistamine blockade of alcohol-induced flushing in orientals. J Stud Alcohol. 1988 Jan;49(1):16-20. doi: 10.15288/jsa.1988.49.16.
- Background: PubMed 720389Altura BM, Carella A, Altura BT. Acetaldehyde on vascular smooth muscle: possible role in vasodilator action of ethanol. Eur J Pharmacol. 1978 Nov 1;52(1):73-83. doi: 10.1016/0014-2999(78)90023-7.
- Derived from this study: PubMed 31799996Yu WY, Lu B, Tan D, Aroyan C, Shinkai K, Leslie KS, Fox LP, Yu S, Neuhaus IM, Grekin RC, Arron ST. Effect of Topical Brimonidine on Alcohol-Induced Flushing in Asian Individuals: A Randomized Clinical Trial. JAMA Dermatol. 2020 Feb 1;156(2):182-185. doi: 10.1001/jamadermatol.2019.3508.
- Individual participant dataSharing planned: No
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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.
Wesley Yu, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Brimonidine Tartrate in people with Flushing and Alcohol-Related Disorders, run by University of California, San Francisco at 1 site 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 10 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 4 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Clinician Erythema Score (time frame: Evaluated 30 minutes after alcohol consumption). The study lists 2 primary outcomes in all. 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 NCT03497442, which also lists 5 linked publications.
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 4 May 2020.