By Dr. Catherine M. Legaspi, MD, FPDS
Dr. Concepcion Esto, MD, DPDS
Dr. Madelaine M. Palmea, MD, DPCP
Abstract:
Oleia Oil was compared with 0.09 NaCl solution on dermal safety, as regards photoallergenicity and development of adverse reactions during usage. The 84 panelists showed no significant effect on dermal irritant scoring (p<0.001, Fischer exact test).
The study demonstrated that Oleia, a topical pain relief containing cetylated fatty acids have no skin contact sensitization potentials nor skin photoallergic potentials. The results of the 10-week clinical study did not demonstrate any cumulative irritancy among the 84 volunteers.
Therefore, the utility of Oleia is very promising, as it is mild, well tolerated and safe in the skin. Its dermal effect is comparable to a simple normal saline solution.
CLINICAL TRIAL
Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing Omega-3, Omega-5 And Omega-9 Cetylated Fatty Acid
Catherine M. Legaspi, MD, FPDS
Concepcion Esto, MD, DPDS; Madelaine M. Palmea, MD, DPCP
July 2016
Background:
Topical painkillers or analgesics are rubbed on the skin over painful muscles or joints. Although all are designed to relieve pain, different products use different ingredients and some of them are counterirritants because they create a burning or cooling sensation that distracts the brain from the pain. However, the concern of the increasing contact dermatitis from tropical pain relievers has underscored the need to find a safer alternative. Objectives:
This study aims to determine and compare the dermal safety of OLEIA Omega 3, 5, and 9 cetylated oil with 0.09 NaCl solution (Placebo) in the treatment of muscle and joint pains.
To determine the photoallergic potential of OLEIA Oil in the treatment of muscle and joint pains.
To monitor the development of adverse reactions during product usage over the duration of the study.
Results:
A total of eighty-four panelists completed the treatment protocol. OLEIA Oil and 0.09 NaCl solution-treated patients showed equal results with no significant effect on the dermal irritant scoring in all parameters evaluated (p<0.001, Fisher exact test). Conclusion:
This study showed that OLEIA Cetylated Oil is dermal-safe, no irritant potential and well tolerated in the local skin treatment of muscle and joint pains. Key words:
topical analgesics, contact irritant, photoallergic potential, cetylated oil, randomized controlled trial
Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing Omega-3, Omega-5 And Omega-9 July 2016 Cetylated Fatty Acid
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INTRODUCTION
Despite technological advances and thorough established treatments, pain management continues to defy health professionals. The difficulties that restrict therapeutic success such as increasing systemic side effects and cognitive impairment of oral analgesics are the ultimate motivators for the development of topical preparations.
Topical analgesics or anaesthetics are defined as liquids, gels, powders, creams, semisolids, emulsions, patches, foams, or aerosols containing an analgesic or anaesthetic agent. These topical pain killers are rubbed onto the skin over painful muscles or joints. Although all are designed to relieve pain, different products use different ingredients. And some of these are counterirritants because they create a burning or cooling sensation that distracts the mind from the pain. Most of counterirritants are chemicals that can have potential dermal injury.
The increasing unintentional injuries represent a leading cause of morbidity and mortality around the world for people of all age groups. Dermal safety is one of the most understudied areas of public health (Krejci-Manwaring, Kerchner, Feldman, Rapp & Rapp, 2006) despite recent research documenting that dermatological threats are on the rise worldwide (Jardine et al., 2012). While exposure to ambient solar radiation among vulnerable populations accounts for a large proportion of skin traumas in the form of cancer (Armstrong & Kricker, 2001; Mahé, Ly, Aymard & Dangou, 2003) many other potential skin hazards also exist such as occupational-related skin exposures (National Institute for Occupational Safety and Health, n.d.), community skin exposures and skin damage resulting from practices such as frequent rubbing of muscle and joint pain relievers. Considering the potential harm that can occur from exposure to hazardous chemicals,
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Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing Omega-3, Omega-5 And Omega-9 July 2016 Cetylated Fatty Acid
comparatively little research attention has been given to the widespread global practice of topical analgesics. It is the purpose of this study to initiate skin safety evaluations of topical analgesics and to inspire pharmaceuticals and drug developers to partner with skin authorities (PDS doctors) in insuring dermal safety (the absence of contact sensitization, phototoxicity, cumulative irritancy and hazardous effects) as part of the present standard of care.
METHODOLOGY
A single-blind (outcome assessment), randomized, interventional parallel assignment, and a placebo-controlled clinical trial were conducted over a 10-week period beginning July to September 2016 in three multi-center OPD clinics (NEGH-QC, HealthHub-Makati and MMP Health Clinic-Clark).
One hundred two panelists, ages 18-70 were recruited mostly from community and health work forces (nurses, security guards, janitors, laboratory technicians and construction workers).
The inclusion and exclusion criteria were as follows:
Inclusion Criteria
- Healthy male or female volunteers aged at least 18 years.
Good general, physical and mental health in the opinion of the investigator or medically qualified designee.
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Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing Omega-3, Omega-5 And Omega-9 July 2016 Cetylated Fatty Acid
No clinically significant and relevant abnormalities in medical history or upon physical examination.
Absence of any condition that could affect the volunteer’s safety or well-being or their ability to understand and follow study procedures and requirements.
Healthy volunteers who do not have excessive hair o the volar aspect of the forearm(s).
Healthy volunteers should understand and be willing to fully comply with all study procedures and restrictions.
Demonstrates understanding of the study and willingness to participate as evidenced by voluntary written informed consent and has received a signed and dated copy of the informed consent form.
Females of childbearing potential, using an effective contraceptive method for at least one month before the beginning of the study, and willing to use throughout the study.
Exclusion Criteria
Volunteers having recent history (within one year) of alcohol or other substance abuse as determined by medical history.
Participation in another clinical study or receipt of an investigational drug within 30 days of the screening visit.
Previous participation in similar study with similar products.
Volunteer has any visible skin disease at the site of application that, in the opinion of the investigator, will interfere with the skin
assessments.
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Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing Omega-3, Omega-5 And Omega-9 July 2016 Cetylated Fatty Acid
Volunteer has current or relevant previous history of serious, severe or unstable physical or psychiatric illness, or medical disorders such as current or previous history of hepatic or renal diseases (impairment) or peptic ulcer as determined by medical history.
Volunteer has a history of hypersensitivity (e.g. asthma, bronchospasm, rhinitis, urticaria, nasal polyps) to aspirin, diclofenac, other nonsteroidal anti-inflammatory drugs (NSAIDs), menthol or any of the excipients in the test product(s).
Volunteer is receiving systemic or topical NSAIDs, other oral or topical analgesics or antihistamine within 3 days of visit 1, or other medication (such as corticosteroids within 3 weeks of visit 1) which, in the opinion of the investigative personnel, will interfere with the study results.
Female volunteers who are pregnant, planning to become pregnant during the study or are breastfeeding.
Female volunteers who have positive pregnancy test.
Volunteers who are employees of the sponsor or study site or an immediate family member (e.g. partner, offspring, parents, siblings or
sibling’s offspring) of such employees.
Any skin disorder at the test site that in the investigator’s judgement
can affect the readings of the test result.
Any concomitant medications that in the investigator’s judgement can
confound or alter test results or evaluation of the adverse events.
Once the subject was deemed eligible for the study, nature of the study was explained to the subjects. The consent form was explained and duly signed by the subject. The subjects were randomly distributed to one of the two study groups using a randomization code generated from CLINSTAT software.
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Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing Omega-3, Omega-5 And Omega-9 July 2016 Cetylated Fatty Acid
Intervention: The first 32 subjects/panelists were requested to undergo the 3-leveled study group (1) Primary Irritancy Test, (2) Photo Allergic Potential Test, (3) Cumulative Irritancy Test. The remaining recruits proceeded immediately to the Cumulative Irritancy Test.
Subjects enrolled in Primary Irritancy Test were randomly distributed to the OLEIA Group and Placebo Group (0.9 NaCl solution). The investigator put one drop of the solution on the right forearm which was then sealed with Tegaderm plaster. They were requested to have the 24-hour patch test. They were requested to return on the following day for the investigators to record the results.
After applying the Tegaderm plaster on the right forearm, the subjects/panelists proceeded to the Photo Allergic Potential Test. Using their previous randomized grouping, a drop of the solution was put on the left forearm and exposed with UVB light for 5 minutes. Results were recorded immediately after the 5-minute test.
All panelists were subsequently enrolled in the Cumulative Irritancy Test. They were instructed to apply the given solution liberally over aching joints and muscles and instructed to report immediately if any irritations were noted. They were also told to come and follow up weekly for two weeks.
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Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing Omega-3, Omega-5 And Omega-9 July 2016 Cetylated Fatty Acid
OUTCOME MEASUREMENTS
The primary outcome measured was the absence of clinical signs of dermal irritation including (1) skin turning red, (2) welting up, (3) showing a rash, (4) oozing skin, (5) symptoms of itchiness on the body sites where the solution was applied. A standard severity grading scale (0=absent, 1=mild, 2=moderate, 3=severe) was used to rate each sign and symptom. The panelists were required to note and report any other adverse side effects using a standard questionnaire.
STANDARD ANALYSIS
All statistical computations were conducted using SPSS software. Demographic variables and other baseline characteristics were summarized by descriptive statistics. The Chi-Square test without continuity correction was used to analyze discrete variables, and analysis of variance was used for continuous variables to assess comparability among the two treatment groups. Further, a Fisher’s exact test was used to test the difference. All statistical tests were two-tailed with a significance level of alpha=0.05.
RESULTS
A total of 102 panelists were recruited for this clinical trial but only 84 completed the treatment protocol and were included in the analysis. The panelists were randomized to receive placebo (0.09 NaCl Solution) and OLEIA. Of the first 32 recruits that underwent the Primary Irritancy Group, 27 (15 for OLEIA and 12 for Placebo) completed the 24-hour patch test.
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Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing Omega-3, Omega-5 And Omega-9 Cetylated Fatty Acid
July 2016
- PRIMARY IRRITANCY GROUP Table I: Demographic
OLEIA GROUP PLACEBO 7 7 85 39.92 39.69
p value 0.884
0.915
Characteristics
Gender M
F
Mean Age
Table I shows the demographics that there were no significant differences among the treatment groups with regard to gender and age.
The panelists were evaluated after 24 hours for the dermal irritancy scoring (Table II). All or 100% of the panelists on both groups did not develop skin redness, welting up, rash, oozing skin nor any symptoms of itchiness.
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Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing Omega-3, Omega-5 And Omega-9 July 2016 Cetylated Fatty Acid
Table II: Dermal Irritant Score
0-Absent 1-Mild 2-Moderate 3-Severe
0 15 (100%) 0 11 22 33 0 15 (100%) 0 11 22 33 0 15 (100%) 0 11 22 33 0 15 (100%) 0 11 22 33 0 15 (100%) 0 11 22 33
12 (100%)
12 (100%)
12 (100%)
12 (100%)
12 (100%)
OLEIA
PLACEBO
Skin turning red
Welting up
Showing a rash
Oozing skin
Symptoms of itchiness
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Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing Omega-3, Omega-5 And Omega-9 July 2016 Cetylated Fatty Acid
The same group was enrolled in the second test which is the Photocontact Irritant Potential, wherein a drop of the solution is put on the left forearm and exposed to UVB light for 5 minutes. The 32 panelists completed the test.
- PHOTOCONTACT IRRITANT POTENTIAL GROUP Table III: Demographic
OLEIA GROUP PLACEBO 7 10 96 40.06 41.31
p value 0.800
0.818
Characteristics
Gender M
F Mean Age
Table III showed that there were no significant differences among the treatment groups for gender and age.
Of the 32 panelists showed in Table IV, none of them developed redness, welting, oozing, skin rash or developed itchiness. However, one patient developed post procedure pigmentation that went away spontaneously without any intervention after 5 days.
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Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing Omega-3, Omega-5 And Omega-9 July 2016 Cetylated Fatty Acid
Table IV: Dermal Irritant Score
0-Absent 1-Mild 2-Moderate 3-Severe
0 16 (100%) 0 11 22 33 0 16 (100%) 0 11 22 33 0 16 (100%) 0 11 22 33 0 16 (100%) 0 11 22 33 0 16 (100%) 0 11 22 33
16 (100%)
16 (100%)
16 (100%)
16 (100%)
16 (100%)
OLEIA
PLACEBO
Skin turning red
Welting up
Showing a rash
Oozing skin
Symptoms of itchiness
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Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing Omega-3, Omega-5 And Omega-9 July 2016 Cetylated Fatty Acid
III. CUMULATIVE IRRITANT GROUP
Eighty four panelists were evaluated for the cumulative irritancy test for 2 weeks. They were monitored after 24 hours, after 1 week and after 2 weeks. During each visit, skin conditions were analyzed using the scoring pattern. All the data were statistically analyzed using Wilcoxon Signed Rank Test.
Table V: Demographic
Characteristics
Gender M
F Mean Age
OLEIA GROUP 25
PLACEBO p value 24 0.800
33.81
36.58 0.915
18 17
Table V shows that there were no significant differences in demographic and baseline characteristics of the panelists.
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Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing Omega-3, Omega-5 And Omega-9 Cetylated Fatty Acid
Table VI: Skin Turning Red
Dermal Irritant Score
0-Absent 1-Mild 2-Moderate 3-Severe
July 2016
Score
Day 1 OLEIA
Day 1 Placebo
Day 7 OLEIA
Day 7 Placebo
Day 14 OLEIA
Day 14 Placebo
0
1 2 3
43/43 41/41 43/43 41/41 43/43 000000 000000 000000
On Day1, Day7 and Day14, no panelists developed skin redness on both study groups. No significant differences between the OLEIA and the placebo groups were noted.
Table VII: Welting Up
43/43 41/41 43/43 41/41 43/43 41/41 000000 000000 000000
On Day1, Day7 and Day14, no panelists developed skin welting up on both study groups. No significant differences between the OLEIA and the placebo groups were noted.
41/41
Score
Day 1 OLEIA
Day 1 Placebo
Day 7 OLEIA
Day 7 Placebo
Day 14 OLEIA
Day 14 Placebo
0 1 2
3
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Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing Omega-3, Omega-5 And Omega-9 July 2016 Cetylated Fatty Acid
Table VIII: Skin Showing A Rash
43/43 41/41 43/43 41/41 43/43 41/41 000000 000000 000000
On Day1, Day7 and Day14, no panelists developed skin rashes on both study groups. No significant differences between the OLEIA and the placebo groups were noted.
Table IX: Oozing Skin
43/43 41/41 43/43 41/41 43/43 41/41 000000 000000 000000
On Day1, Day7 and Day14, no panelists developed oozing skin on both study groups. No significant differences between the OLEIA and the placebo groups were noted.
Score
Day 1 OLEIA
Day 1 Placebo
Day 7 OLEIA
Day 7 Placebo
Day 14 OLEIA
Day 14 Placebo
0 1 2 3
Score
Day 1 OLEIA
Day 1 Placebo
Day 7 OLEIA
Day 7 Placebo
Day 14 OLEIA
Day 14 Placebo
0 1 2 3
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Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing Omega-3, Omega-5 And Omega-9 July 2016 Cetylated Fatty Acid
Table X: Symptoms Of Itchiness
43/43 41/41 43/43 41/41 43/43 41/41 000000 000000 000000
On Day1, Day7 and Day14, no panelists developed symptoms of itchiness on both study groups. No significant differences between the OLEIA and the placebo groups were noted.
There was no systemic adverse effect reported except for one case who developed post UVB light hyperpigmentation but subsequently resolved after five days of no intervention.
Score
Day 1 OLEIA
Day 1 Placebo
Day 7 OLEIA
Day 7 Placebo
Day 14 OLEIA
Day 14 Placebo
0 1 2 3
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Local Skin Safety Of Topical Pain Relief Oil (OLEIA) Containing Omega-3, Omega-5 And Omega-9 July 2016 Cetylated Fatty Acid
CONCLUSION
This study demonstrated that OLEIA Oil, a topical pain relief containing cetylated fatty acids have no skin contact sensitization potentials nor skin photoallergic potentials.
The results of the 10-week clinical study failed to demonstrate any cumulative irritancy on all the 84 volunteers.
Both OLEIA and Placebo (0.09 NaCl) showed no statistical difference.
Therefore, the utility of OLEIA Oil is very promising as it is mild, well tolerated and safe on the skin. Its dermal effect is comparable to a simple normal saline solution.
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