Relationship of Whole Blood Zinc Levels to Acne Severity

Acne Vulgaris Clinical Trial

Official title:

Relationship of Whole Blood Zinc Levels to Acne Severity Among Filipinos 18-25 Years Old: A Cross-sectional Comparative Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04975412
• Other study ID #: EAMC IERB 2017-40
• Status: Completed
• Start date: November 27, 2017
• Est. completion date: March 16, 2018

Study information

• Verified date: July 2021
• Source: East Avenue Medical Center, Philippines
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Acne Vulgaris is one of the most common dermatologic diagnoses in the world. A number of studies have been conducted comparing serum zinc levels with acne vulgaris; however, no studies have yet been done in the Philippine setting.

The objective of this study is to determine the relationship between whole blood zinc levels and the severity of acne vulgaris in Filipino patients and normal controls who are 18-25 years old.

Description:

Acne Vulgaris is a disorder of the pilosebaceous unit characterized by formation of comedones, papules, pustules, inflamed nodules, and cysts.1 Most common predilection sites are those with hormonally sensitive sebaceous glands such as the face, neck, chest, upper back and upper arms. Acne can persist for years and result in disfigurement and permanent scarring. It can cause serious adverse effects on psychosocial development, resulting in emotional problems, withdrawal from society, and depression. Nearly all adolescents experience different severity levels of acne vulgaris, with moderate to severe levels affecting around 20% of this population. In the Philippines, high school students were found to have a mild impairment of quality of life (QOL) due to acne, regardless of severity. Despite the known treatment regimens for acne, people are still suffering from the effects of the disease.

Acne has four main pathogenic contributors: follicular hyperkeratinization, increased sebum production, Propionibacterium acnes (P. acnes) within the follicle, and inflammation. Reports show that antibiotic resistance is a growing issue in the treatment regimen of acne vulgaris, making it less and less suitable for long-term treatment. Other options that can be substitutes or adjuncts to treatment may be useful in this condition.

Zinc is an essential element for normal epithelial differentiation and for normal development. It has also been shown to have antioxidant properties. At present, there is paucity of data regarding the role of zinc levels in the development or severity of acne vulgaris. Also, data on favorable effects of dietary factors such as zinc, omega-3 fatty acids, antioxidants, vitamin A, and dietary fiber on acne vulgaris are limited specially in the Philippines.

This study will be conducted to measure the whole blood zinc levels in patients with acne vulgaris and compare it with healthy controls. This aims to determine the relationship between whole blood zinc levels and disease severity in Filipino patients with acne vulgaris in order to bring new insight to guide further studies regarding zinc's role in the pathogenesis and possible further treatment of acne vulgaris in the Philippines.

Significance of the Study:

While a number of studies have been conducted comparing serum zinc levels with acne vulgaris, no previous studies have been done in the Philippine setting that assesses the relationship of whole blood zinc levels with the severity of acne. Given that acne vulgaris is one of the most common dermatologic diagnoses in the Philippine population, and the increasing resistance to antibiotics commonly used to treat acne, studies about other treatment modalities for acne vulgaris that do not have resistance factors are timely and significant in the country.

For long-term or maintenance therapy, physicians should consider effectivity, cost, and adverse effects. By determining the relationship of whole blood zinc levels to acne severity among Filipinos 18-25 years old, this study can be used as evidence for giving zinc supplements to Filipino people diagnosed with acne vulgaris if a significant relationship is found. Since zinc is more cost-effective and has less adverse effects compared to most antibiotics, this may prove helpful for the Filipino patient in terms of safety and economy for long-term therapy. Furthermore, this study may also be able to provide more information for further studies towards non-antimicrobial treatment regimens for acne vulgaris in the Philippines.

Research Question:

Is there a relationship between whole blood zinc levels and the severity of acne vulgaris in Filipino patients 18-25 years old versus normal controls?

Null Hypothesis: There is no relationship between whole blood zinc levels and the severity of acne vulgaris.

Alternative Hypothesis: There is a relationship between whole blood zinc levels and the severity of acne vulgaris.

Objectives:

• To study the relationship between whole blood zinc levels and the severity of acne vulgaris in Filipino patients 18-25 years old and normal controls

• To describe the clinical profile of Filipino patients 18-25 years old with acne vulgaris

• To determine the whole blood zinc levels of acne patients compared to controls

• To determine the relationship of the clinical severity of acne vulgaris to whole blood zinc levels

A cross-sectional comparative study design will be utilized for this study which will be conducted from November 2017 to March 2018. The study will be conducted at the Dermatology Out-patient Clinic of the East Avenue Medical Center (EAMC).

STUDY PROCEDURE

1. The study will be submitted to the Technical Review Board and Institution Ethics and Review Board for approval.

2. In the Dermatology Out-Patient Department of East Avenue Medical Center, patients seeking consult for their skin lesions which were diagnosed to be Acne Vulgaris will be screened if they meet the inclusion/exclusion criteria.

3. Informed consent will be obtained for those who are qualified.

4. Patients will be given proper treatment whether they agree to participate or not. For the patients who agree to participate, the investigator will assess the patient's acne severity using the Global Acne Grading Scale (GAGS).

5. Twelve milliliters of blood will be extracted from the patient with proper aseptic technique and waste disposal.

6. Blood sample will be properly stored in three EDTA tubes, labelled, and transported to the laboratory for determination of whole blood zinc levels through ashing acid digestion- inductively coupled plasma (ICP) using Shimadzu ICPS-7510, an inductively coupled plasma emission spectrometer.

1. Blood samples are viable and stable for 5 days at 15-25 degrees Celsius.

2. A memorandum of agreement between the principal investigator and Hi-Precision Diagnostics, Inc. has been made. Hi-Precision Diagnostics will be providing the materials for extraction, picking-up, and transporting the blood sample using a special insulated medical specimen bag (Versapak Pathology and Specimen bag) with ice packs and thermometer to help maintain the ideal temperature of 15-25 degrees Celsius.

3. Schedule of specimen pick-up is from 8:00 am- 8:00 pm and may be done on an as-needed basis. The blood specimens will be stored in the refrigerator immediately after extraction.

7. Results will be obtained by the investigator via the online results portal of the laboratory.

8. Data collected will be tabulated and data analysis will be done.

PASS 2008 was used for the computation of minimum sample size. Parameters for the computation was obtained from previously published studies. For the one-way ANOVA, a minimum of 40 patients (10 for each acne severity: mild, moderate and severe acne and 10 for controls) achieves 95% power to detect differences among the means versus the alternative of equal means using an F test with a significance level of 0.05. The size of the variation in the means is represented by their standard deviation which is 13.30 mg/dL and the common standard deviation within a group is assumed to be 20.00 mg/dL.

Data will be encoded by the researcher in MS Excel. The excel file will be converted into Stata file for further data processing and analysis. Stata SE version 12 will be used for both descriptive and inferential statistics. Quantitative variables will be presented as mean or median while qualitative variables will be presented as percentages.

In order to compare the whole blood zinc levels between cases and controls, independent T-test will be used. ANOVA will be used to compare the whole blood zinc levels by acne severity. Multiple linear regression analysis will then be performed in order to determine the association of whole blood zinc levels with acne severity after controlling for the effects of significant confounding variables. All p values ≤ 0.05 will be considered as significant.

The correlation of whole blood zinc levels with severity of acne vulgaris in Filipino patients may help clinicians recommend more detailed dietary advice and add non-antibiotic supplements to their current treatment of acne vulgaris. The results of the study can serve as a guide for further studies related to whole blood zinc and its role in the pathogenesis of acne vulgaris in Filipino patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 16, 2018
• Est. primary completion date: March 16, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 25 Years

Eligibility

Inclusion Criteria for cases:

• Filipino patients, aged 18-25 years old

• Diagnosis of acne vulgaris

• Able to read and write in English or Tagalog

• Seen at the dermatology out-patient department of East Avenue Medical Center

Exclusion Criteria for cases:

• Patients with other chronic dermatoses or systemic disease

• Taking oral supplements or medications for the past 3 months

• Patients who are pregnant or lactating

Inclusion Criteria for controls:

• Filipino patients, aged 18-25 years old

• Able to read and write in English or Tagalog

• Seen at the dermatology out-patient department of East Avenue Medical Center

Exclusion Criteria for controls:

• Patients with acne vulgaris or other chronic dermatoses or systemic disease

• Taking oral supplements or medications for the past 3 months

• Patients who are pregnant or lactating

Related Conditions & MeSH terms

• Acne Vulgaris

Intervention

Diagnostic Test:
• Whole blood zinc level
whole blood zinc levels determined through ashing acid digestion-inductively coupled plasma (ICP) using Shimadzu ICPS-7510, an inductively coupled plasma emission spectrometer.

Locations

Country	Name	City	State
Philippines	East Avenue Medical Center	Quezon CIty	Metro Manila

Sponsors (1)

Lead Sponsor	Collaborator
East Avenue Medical Center, Philippines

Country where clinical trial is conducted

Philippines, 

References & Publications (33)

Adityan B, Kumari R, Thappa DM. Scoring systems in acne vulgaris. Indian J Dermatol Venereol Leprol. 2009 May-Jun;75(3):323-6. doi: 10.4103/0378-6323.51258. Review. — View Citation

Akhtar S. Zinc status in South Asian populations--an update. J Health Popul Nutr. 2013 Jun;31(2):139-49. Review. — View Citation

Al-Shobaili HA. Oxidants and anti-oxidants status in acne vulgaris patients with varying severity. Ann Clin Lab Sci. 2014 Spring;44(2):202-7. — View Citation

Amer M, Bahgat MR, Tosson Z, Abdel Mowla MY, Amer K. Serum zinc in acne vulgaris. Int J Dermatol. 1982 Oct;21(8):481-4. — View Citation

Arora PN, Dhillon KS, Rajan SR, Sayal SK, Das AL. Serum Zinc Levels in Cutaneous Disorders. Med J Armed Forces India. 2002 Oct;58(4):304-6. doi: 10.1016/S0377-1237(02)80083-1. Epub 2011 Jul 21. — View Citation

Aydemir EH. Acne vulgaris. Turk Pediatri Ars. 2014 Mar 1;49(1):13-6. doi: 10.5152/tpa.2014.1943. eCollection 2014 Mar. Review. — View Citation

Bhate K, Williams HC. Epidemiology of acne vulgaris. Br J Dermatol. 2013 Mar;168(3):474-85. doi: 10.1111/bjd.12149. Review. — View Citation

Bray TM, Bettger WJ. The physiological role of zinc as an antioxidant. Free Radic Biol Med. 1990;8(3):281-91. Review. — View Citation

Buxaderas SC, Farré-Rovira R. Whole blood and serum zinc levels in relation to sex and age. Rev Esp Fisiol. 1985 Dec;41(4):463-70. — View Citation

Canavan TN, Chen E, Elewski BE. Optimizing Non-Antibiotic Treatments for Patients with Acne: A Review. Dermatol Ther (Heidelb). 2016 Dec;6(4):555-578. Epub 2016 Aug 19. Review. — View Citation

Collier CN, Harper JC, Cafardi JA, Cantrell WC, Wang W, Foster KW, Elewski BE. The prevalence of acne in adults 20 years and older. J Am Acad Dermatol. 2008 Jan;58(1):56-9. Epub 2007 Oct 22. Erratum in: J Am Acad Dermatol. 2008 May;58(5):874. Cafardi, Jennifer A [added]. — View Citation

Cooper AJ. Systematic review of Propionibacterium acnes resistance to systemic antibiotics. Med J Aust. 1998 Sep 7;169(5):259-61. Review. — View Citation

Eady EA, Cove JH, Holland KT, Cunliffe WJ. Erythromycin resistant propionibacteria in antibiotic treated acne patients: association with therapeutic failure. Br J Dermatol. 1989 Jul;121(1):51-7. — View Citation

Eady EA, Gloor M, Leyden JJ. Propionibacterium acnes resistance: a worldwide problem. Dermatology. 2003;206(1):54-6. Review. — View Citation

Goulden V, Stables GI, Cunliffe WJ. Prevalence of facial acne in adults. J Am Acad Dermatol. 1999 Oct;41(4):577-80. — View Citation

Gupta M, Mahajan VK, Mehta KS, Chauhan PS. Zinc therapy in dermatology: a review. Dermatol Res Pract. 2014;2014:709152. doi: 10.1155/2014/709152. Epub 2014 Jul 10. Review. — View Citation

Humphrey S. Antibiotic resistance in acne treatment. Skin Therapy Lett. 2012 Oct;17(9):1-3. Review. — View Citation

Ikaraoha CI, Mbadiwe NC, Anyanwu CJ, Odekhian J, Nwadike CN, Amah HC. The Role of Blood Lead, Cadmium, Zinc and Copper in Development and Severity of Acne Vulgaris in a Nigerian Population. Biol Trace Elem Res. 2017 Apr;176(2):251-257. doi: 10.1007/s12011-016-0839-4. Epub 2016 Sep 6. — View Citation

Leyden JJ, McGinley KJ, Cavalieri S, Webster GF, Mills OH, Kligman AM. Propionibacterium acnes resistance to antibiotics in acne patients. J Am Acad Dermatol. 1983 Jan;8(1):41-5. — View Citation

Lim KH, Riddell LJ, Nowson CA, Booth AO, Szymlek-Gay EA. Iron and zinc nutrition in the economically-developed world: a review. Nutrients. 2013 Aug 13;5(8):3184-211. doi: 10.3390/nu5083184. Review. — View Citation

Maret W. Zinc biochemistry: from a single zinc enzyme to a key element of life. Adv Nutr. 2013 Jan 1;4(1):82-91. doi: 10.3945/an.112.003038. Review. — View Citation

Michaëlsson G, Vahlquist A, Juhlin L. Serum zinc and retinol-binding protein in acne. Br J Dermatol. 1977 Mar;96(3):283-6. — View Citation

Oteiza PI. Zinc and the modulation of redox homeostasis. Free Radic Biol Med. 2012 Nov 1;53(9):1748-59. doi: 10.1016/j.freeradbiomed.2012.08.568. Epub 2012 Aug 25. Review. — View Citation

Ozuguz P, Dogruk Kacar S, Ekiz O, Takci Z, Balta I, Kalkan G. Evaluation of serum vitamins A and E and zinc levels according to the severity of acne vulgaris. Cutan Ocul Toxicol. 2014 Jun;33(2):99-102. doi: 10.3109/15569527.2013.808656. Epub 2013 Jul 5. — View Citation

Plum LM, Rink L, Haase H. The essential toxin: impact of zinc on human health. Int J Environ Res Public Health. 2010 Apr;7(4):1342-65. doi: 10.3390/ijerph7041342. Epub 2010 Mar 26. Review. — View Citation

Prasad AS. Zinc is an Antioxidant and Anti-Inflammatory Agent: Its Role in Human Health. Front Nutr. 2014 Sep 1;1:14. doi: 10.3389/fnut.2014.00014. eCollection 2014. Review. — View Citation

Rangan AM, Samman S. Zinc intake and its dietary sources: results of the 2007 Australian National Children's Nutrition and Physical Activity Survey. Nutrients. 2012 Jul;4(7):611-24. doi: 10.3390/nu4070611. Epub 2012 Jun 26. — View Citation

Ross JI, Snelling AM, Carnegie E, Coates P, Cunliffe WJ, Bettoli V, Tosti G, Katsambas A, Galvan Peréz Del Pulgar JI, Rollman O, Török L, Eady EA, Cove JH. Antibiotic-resistant acne: lessons from Europe. Br J Dermatol. 2003 Mar;148(3):467-78. — View Citation

Rostami Mogaddam M, Safavi Ardabili N, Maleki N, Soflaee M. Correlation between the severity and type of acne lesions with serum zinc levels in patients with acne vulgaris. Biomed Res Int. 2014;2014:474108. doi: 10.1155/2014/474108. Epub 2014 Jul 24. — View Citation

Rostan EF, DeBuys HV, Madey DL, Pinnell SR. Evidence supporting zinc as an important antioxidant for skin. Int J Dermatol. 2002 Sep;41(9):606-11. Review. — View Citation

Sardana K, Chugh S, Garg VK. The role of zinc in acne and prevention of resistance: have we missed the "base" effect? Int J Dermatol. 2014 Jan;53(1):125-7. doi: 10.1111/ijd.12264. — View Citation

Tan JK, Bhate K. A global perspective on the epidemiology of acne. Br J Dermatol. 2015 Jul;172 Suppl 1:3-12. doi: 10.1111/bjd.13462. Review. — View Citation

Toyoda M, Morohashi M. Pathogenesis of acne. Med Electron Microsc. 2001 Mar;34(1):29-40. Review. — View Citation

* Note: There are 33 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acne severity	Based on the Global Acne Grading System (GAGS) score. Minimum value 0, maximum value 44. Acne severity is rated as mild (1-18), moderate (19-30), severe (31-38), and very severe (=39). Control patients have GAGS score of 0.	initial consult
Primary	Whole blood zinc level	whole blood zinc level in µg/mL	initial consult
Secondary	demographics	age and sex	initial consult

External Links

•   A Cross-Sectional Study on the Impact of Acne Vulgaris on the Quality of Life among High School Students in Pasig City, Philippines
•   Ashing of organic samples and determination of Zn and Fe using inductively coupled plasma atomic emission spectroscopy (ICP-AES) method
•   Dietary sources of zinc and factors affecting its bioavailability
•   Effect of Serum Trace Elements, Macro-minerals and Antioxidants in Acne Vulgaris Patients: A Case-Control Study
•   Serum Trace Elements (Zinc, Copper and Magnesium) Status in Iraqi Patients with Acne Vulgaris:( Case- Controlled Study)
•   Toxicological profile for zinc
•   Zinc Levels in Patients with Acne Vulgaris
•   Zinc Status of Filipinos by Serum Zinc Level