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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Brimonidine Tartrate | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Evaluated 30 minutes after alcohol consumption |
| Patient Erythema Self Assessment | Subject self-assessment 0: No signs of unwanted redness
| Evaluated 30 minutes after alcohol consumption |
| Measure | Description | Time Frame |
|---|---|---|
| Delayed Clinician Erythema Score | Clinician Erythema Assessment (CEA) Scale | Evaluated 60 and 90 minutes after alcohol consumption |
| Delayed Patient Erythema Self Assessment | Subject self-assessment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wesley Yu, MD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC, San Francisco | San Francisco | California | 94115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19320537 | Background | 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. | |
| 17718397 | Background | Eng MY, Luczak SE, Wall TL. ALDH2, ADH1B, and ADH1C genotypes in Asians: a literature review. Alcohol Res Health. 2007;30(1):22-7. |
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| ID | Term |
|---|---|
| D005483 | Flushing |
| D019973 | Alcohol-Related Disorders |
| ID | Term |
|---|---|
| D012877 | Skin Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D019966 | Substance-Related Disorders |
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| ID | Term |
|---|---|
| D000068438 | Brimonidine Tartrate |
| ID | Term |
|---|---|
| D011810 | Quinoxalines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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This is a split face study. All participants will follow an identical protocol with active medication applied to half of their face and placebo applied to the other half. Treatment and placebo side will be randomized.
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| Placebo Vehicle Gel | Drug | Vehicle Gel |
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| Evaluated 60 and 90 minutes after alcohol consumption |
| 3347071 | Background | Miller 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. |
| 720389 | Background | Altura 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. |
| 31799996 | Derived | Yu 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. |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |