Weekly Isotretinoin Therapy for the Treatment of Moderate Acne Vulgaris
Phase: PHASE1
Conditions: Acne Vulgaris
Sponsor: Medical University of South Carolina

 
 
 
Weekly Isotretinoin Therapy for the Treatment of 
Moderate Acne Vulgaris  
NCT Number: NCT04594759 
11/3/2020 

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PROTOCOL TITLE: 
Weekly Isotretinoin Therapy for the Treatment of Moderate Acne Vulgaris  
SHORT TITLE: 
WIT Study 
PRINCIPAL INVESTIGATOR: 
Samantha Karlin, MD (MUSC Dermatology resident, PGY3) 
 
 

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1. 
Objectives / Specific Aims 
The objectives of the study are to: 
• determine if once weekly dosed isotretinoin is effective for moderate acne vulgaris 
• evaluate patient satisfaction with once weekly dosed isotretinoin for moderate acne 
vulgaris treatment    
• identify any adverse effects associated with once weekly dosed isotretinoin for 
moderate acne vulgaris treatment 
2.0 
Background 
In current Dermatology practice, options for moderate acne vulgaris remain limited. 
Moderate acne is clinically defined as acne that has not responded to at least three months 
of topical therapy and is not severe enough for initial treatment with a conventional course 
of isotretinoin (formerly known as Accutane). The mainstay of treatment for moderate 
acne remains long courses of oral antibiotics, mainly tetracyclines (doxycycline, 
minocycline) and occasionally trimethoprim-sulfamethoxazole. Males with moderate acne, 
in particular, are especially limited in their treatment options as they are not eligible for 
hormonal management (spironolactone, oral contraceptive pills) like their female 
counterparts. Additionally, even for those regardless of gender who may eventually qualify 
for a traditional isotretinoin course, many insurance companies first require failure to 
respond to at least three months of oral antibiotics. Nagler et. al found that the average 
antibiotic use for moderate to severe acne prior to receiving isotretinoin was 331 days, with 
15.3% of patients prescribed antibiotics for three months or less, 88% for six months or 
more, and 46% for at least one year.1 Despite the widespread use of oral antibiotics in 
acne, antibiotic resistance is considered a global threat per the CDC2, and there have been 
calls to limit their use in acne because of concerns of bacterial resistance3,4,5. Because of 
this, there is a significant need for more research on alternative treatment options for 
moderate acne.  
Once weekly isotretinoin dosing has the potential to significantly improve moderate 
acne with good patient satisfaction and safety profile; however, no study findings on this 
treatment option have been published to date. The efficacy of isotretinoin, an oral vitamin 
A derivative, for treatment of acne has been well established. The traditional treatment 
course for severe acne consists of once to twice daily dosing (0.5-1 mg/kg/day) for 4-7 
months (or 150mg/kg total cumulative dose). Though efficacious, there are numerous 
reported side-effects due to achieving the cumulative dose rapidly by once to twice daily 
dosing, such as severe dry skin, lips, and eyes, as well as liver enzyme and lipid 
abnormalities. Because of this, there have been studies exploring alternative isotretinoin 
dosing regimens including microdose, lower daily dose regimens (0.15-0.4 mg/kg/day6, 
0.25-0.4 mg/kg/day7, 0.3-0.4 mg/kg/day8,9, in addition to 5 mg/day10 and 0.15-0.28 
mg/kg/day with additional of local application of 1% clindamycin gel every other day11) 
and daily dosing for 7-10 consecutive days (0.5-0.7 mg/kg/day) out of each month 
only.7,12,13,14 All studies had favorable outcomes with alternative dosing, despite the lower 
total cumulative dose versus conventional dosing. Those who also analyzed adverse effect 
rates with alternative isotretinoin dosing found that these were either rarely observed or 
similar to conventional dosing.6,8,9,10,12,14 In contrast, the potential adverse effects of oral 
antibiotics used for acne include photosensitivity and nausea/vomiting (doxycycline), 
drug-induced pigment deposition and drug-induced systemic lupus erythematosus 

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(minocycline), and angioedema and drug rashes including drug reaction with eosinophilia 
and systemic symptoms (DRESS) syndrome (trimethoprim-sulfamethoxazole). 
Interestingly, rates of acne recurrence between alternative isotretinoin dosing and 
conventional dosing were similar at follow-up,6,7,9 despite a much older study from 1984 
that found otherwise.15 Additionally, cost of alternative isotretinoin dosing was lower than 
with conventional dosing,8,9,13 and patient satisfaction was highest in the alternative dosing 
groups.7,10 
For these reasons, we propose a study evaluating the efficacy of once weekly 
isotretinoin dosing (1-1.5 mg/kg/week) as a potential alternative to oral antibiotics for the 
treatment of patients with moderate acne. Secondary endpoints include patient satisfaction 
and adverse effects. 
 
1) Nagler AR, Milam EC, Orlow SJ. The use of oral antibiotics before isotretinoin 
therapy in patients with acne. J Am Acad Dermatol. 2016;74(2):273‐279. 
doi:10.1016/j.jaad.2015.09.046 
2) Center for Disease Control (https://www.cdc.gov/drugresistance/biggest-
threats.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fdrugresist
ance%2Fbiggest_threats.html) 
3) Dreno B, Thiboutot D, Gollnick H, et al. Antibiotic stewardship in dermatology: 
limiting antibiotic use in acne. Eur J Dermatol. 2014;24(3):330-334.  
4) Bowe WP. Antibiotic resistance and acne: where we stand and what the future holds. 
J Drugs Dermatol. 2014;13(6): s66-s70.  
5) Ross JI, Snelling AM, Carnegie E, et al. Antibiotic-resistant acne: lessons from 
Europe. Br J Dermatol. 2003;148(3):467-478. 
6) Mandekou-Lefaki I, Delli F, Teknetzis A, et al. Low-dose schema of isotretinoin in 
acne vulgaris. Int J Clin Pharmacol Res. 2003;23:41–6 
7) Lee JW, Yoo KH, Park KY, Han TY, Li K, Seo SJ, Hong CK. Br J Dermatol. 
2011;164(6):1369. Epub 2011 May 17.  
8) Amichai B, Shemer A, Grunwald MH. Low-dose isotretinoin in the treatment of acne 
vulgaris. J Am Acad Dermatol. 2006;54:644–6.  
9) Kotori MG. Low-dose vitamin “A” tablets – treatment of acne vulgaris. Med 
Arch. 2015;69:28–30. 
10)  Rademaker M, Wishart JM, Birchall NM. Isotretinoin 5 mg daily for low-grade adult 
acne – a placebo-controlled, randomized double-blind study. JEADV. 2014;28:747–
54. 
11)  Sardana K, Garg VK, Sehgal VN, et al. Efficacy of fixed low-dose isotretinoin (20 
mg, alternate days) with topical clindamycin gel in moderately severe acne vulgaris. J 
Eur Acad Dermatol Venereol. 2009;23:556–60.  
12)  Akman A, Durusoy C, Senturk M, et al. Treatment of acne with intermittent and 
conventional isotretinoin: a randomized, controlled multicenter study. Arch Dermatol 
Res. 2007;299:467–73. 
13)  Goulden V, Clark SM, McGeown C, Cunliffe WJ. Treatment of acne with 
intermittent isotretinoin. Br J Dermatol. 1997;137:106–8. 
14) Kaymak Y, Ilter N. The effectiveness of intermittent isotretinoin treatment in mild or 
moderate acne. J Eur Acad Dermatol Venereol. 2006;20:1256–60 
15)  Strauss JS, Rapini RP, Shalita AR, et al. Isotretinoin therapy for acne: results of a 
multicenter dose-response study. J Am Acad Dermatol. 1984;10(3):490–496. 
 

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3.0 
Intervention to be studied (if applicable) 
Intervention: once weekly dosing of isotretinoin (1-1.5 mg/kg/week) 
• FDA status: approved for moderate-severe acne vulgaris in ages 12 and older 
• Please see Background for rationale on proposed dosing method 
• Pharmacology: an oral retinoid (vitamin A derivative) that is thought to improve 
acne by decreasing sebaceous gland proliferation and function, though the exact 
mechanism is unknown. It is a lipophilic medication that is bound to plasma 
proteins; eating a high fat meal with the medication increases its bioavailability but 
not its half life (21 hours). It is metabolized into 4-oxo-retinoic acid, 4-oxo-
isotretinoin, and tretinoin. It is excreted through the feces and urine.16 Improvement 
of acne is due to drug accumulation. Drug serum concentration returns to 
physiologic level after about 2 weeks of taking the drug.17 
• Safety: isotretinoin use is most commonly associated with xerosis and chelitis. It 
can more rarely be associated with hypersensitivity reactions, hypertriglyceridemia, 
hepatitis, agranulocytosis, musculoskeletal symptoms, pseudotumor cerebri, mood 
swings including depression, delayed wound healing, hearing impairment, and 
decreased night vision and corneal opacities. It can cause birth defects in women 
who become pregnant while taking the medication. There is a potential association 
with worsening of inflammatory bowel disease.16 Because of this, all patients (men 
and women) who take isotretinoin must enroll in the IPLEDGE program prior to 
administration of medication. 
 
16) FDA drug information, isotretinoin, Roche Laboratories. 
(https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/018662s059lbl.pdf) 
17) Torzecka JD, Dziankowska-Bartkowiak B, Gerlicz-Kowalczuk Z, Wozniacka A. The 
use of isotretinoin in low doses and unconventional treatment regimens in different 
types of acne: a literature review. Postepy Dermatol Alergol. 2017;34(1):1‐5. 
doi:10.5114/ada.2017.65614 
 
4.0 
Study Endpoints (if applicable) 
Primary endpoint: efficacy  
Secondary endpoints: patient satisfaction, adverse effects 
 
5.0 
Inclusion and Exclusion Criteria/ Study Population 
Inclusion Criteria  
• 
English-speaking patients 12 years and older with the diagnosis of moderate 
acne vulgaris 
Exclusion Criteria 
• 
Patients who are at baseline on long-term tetracycline antibiotics, long-term 
trimethoprim-sulfamethoxazole, or on spironolactone for any reason 
• 
Patients who have taken isotretinoin in the past 6 months 

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• 
Patients with hypersensitivity to isotretinoin or to any of its components 
• 
Females who are pregnant, likely to become pregnant, or will be breast-feeding 
during the study period 
• 
Patients with a history of major depression, mania, or psychosis with an active 
episode during the past year including current psychotic symptoms and/or 
current suicidal ideation 
• 
Adult patients with cognitive impairment  
• 
Patients with baseline kidney or liver disease 
• 
Patients with baseline hypertriglyceridemia 
• 
Patients with history of or current pseudotumor cerebri 
• 
Patients with any clinically significant unstable medical condition which could 
pose a risk to the safety of the patient  
• 
Inability or unwillingness of subject or legal guardian/representative to give 
informed consent 
6.0 
Number of Subjects 
Target enrollment is 50 participants to allow for attrition. Minimum expected enrollment is 
30 participants. 
7.0 
Setting 
Study site: outpatient dermatology clinics at MUSC. 
8.0 
Recruitment Methods 
• 
Recruitment will occur during standard of care visits to the Dermatology Clinics 
including its virtual visits.  
• 
The first person to inform eligible patients about the study will be a clinician directly 
involved in the eligible patient’s care. The clinician will first determine if the patient 
may meet criteria (score of 3, moderate acne, on CASS clinical scale as described in 
more detail in section 10.0). If the patient expresses interest in the study, the clinician 
or study co-investigators will approach the patient without coercion and with the 
emphasis on the voluntary aspect of being enrolled in this study. He/she will also be 
told in a caring manner that no matter his/her decision, it will not affect his/her care. 
This discussion will take place either in-person during the patient’s clinic 
appointment or over telephone within one business day of the appointment.  
• 
If the discussion takes place in-person during the clinic appointment, the patient will 
be provided a printed recruitment pamphlet reiterating the information regarding the 
study (attachment A). Eligible patients who agree to participate will sign the study 
consent form. Weight will be obtained. A baseline photograph will be taken and 
uploaded into the patient’s medical chart (Epic). Two baseline surveys (Dermatology 
Life Quality Index survey to assess patient satisfaction and a second survey regarding 
potential isotretinoin adverse effects) will be completed by the patient (attachments B 
and C, respectively). The patient’s clinician will then counsel the patient on 
isotretinoin and IPLEDGE and enroll the patient in the IPLEDGE system following 
all prompts. The clinician will order baseline laboratory blood work (all patients) and 

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urinary pregnancy test (females). Once blood work has returned and is without any 
clinically significant abnormalities (see section 13.0), the weekly isotretinoin (at dose 
1-1.5 mg/kg per week) will be prescribed by the clinician (for males). Females will 
need to wait an additional month to have a second negative pregnancy test before 
starting the medication per IPLEDGE standard of care. After a second negative 
pregnancy test at next monthly visit, the clinician can prescribe the weekly dosed 
isotretinoin. 
• 
For any patient who is seeing his or her provider through a virtual visit and is 
interested in participating in the study, a study investigator can either counsel the 
potential participant in the provider’s clinic (via virtual platform) or can call the 
patient to counsel over the phone. Consent can be obtained electronically (per 
REDCap guidelines). These patients will then have an in-person clinic visit 
scheduled with their provider to enroll in IPLEDGE so that the medication can be 
prescribed. Weight will be obtained. A baseline photograph will be taken and 
uploaded into the patient’s medical chart (Epic). Two baseline surveys (Dermatology 
Life Quality Index survey to assess patient satisfaction and a second survey regarding 
potential isotretinoin adverse effects) will be completed by the patient (attachments B 
and C, respectively). The patient’s clinician will then counsel the patient on 
isotretinoin and IPLEDGE and enroll the patient in the IPLEDGE system following 
all prompts. The clinician will order baseline laboratory blood work (all patients) and 
urinary pregnancy test (females). Once blood work has returned and is without any 
clinically significant abnormalities (see section 13.0), the weekly isotretinoin (at dose 
1-1.5 mg/kg per week) will be prescribed by the clinician (for males). Females will 
need to wait an additional month to have a second negative pregnancy test before 
starting the medication per IPLEDGE standard of care. After a second negative 
pregnancy test at next monthly visit, the clinician can prescribe the weekly dosed 
isotretinoin. 
• 
Additionally, if a study investigator is not available to counsel the patient at the time 
of the patient’s clinic visit, and the clinician believes that the patient may qualify for 
the study, the clinician will send an Epic electronic health record message to the 
Study Coordinator (Dermatology research fellow) with the attached patient chart. The 
Study Coordinator will contact the patient by telephone within one business day. 
Over the phone, the study investigator will assess if the patient is eligible for the 
study and if he/she would like to participate. If so, an additional clinic visit (either in-
person or virtual) will be set up with the patient’s clinician to obtain a baseline 
photograph (alternatively the patient can also upload their own photos into MyChart), 
as well as to enroll the patient into IPLEDGE after counseling on the system and 
isotretinoin medication. Two baseline surveys (attachments B and C) and the study 
consent form (attachment E) will be sent electronically (per REDCap guidelines) for 
signature. These steps are outlined in directions for providers, a pamphlet that will be 
printed in each clinic site (attachment D). The signed consent form and two 
completed surveys can either be emailed back to the Study Coordinator for upload 
into the patient’s medical chart (Epic) or photos of these can be taken by the patient 
for upload into their medical chart via MyChart (Epic). Once the patient is enrolled in 
both the study and IPLEDGE and is medically cleared to start isotretinoin, the 
clinician will prescribe the medication at the weekly study dose. 

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• 
No study-only procedures will be performed without first obtaining informed 
consent. Any standard of care procedures, tests, or visits can be completed at any 
time per clinical care team.  
• 
The study will be posted on the new MUSC Dermatology Research Website. The 
study name, inclusion criteria and brief description of the study design will be posted. 
Patients interested in participating in the study will make an appointment with a 
member of the MUSC Dermatology Team as they must be followed by a 
dermatologist to receive their medication and have labs completed per standard of 
care IPLEDGE protocol.  
9.0 
Consent Process 
• Study consent form is attached (attachment E). The method of obtaining 
consent including where this will take place and how this will be completed is 
detailed in above section 8.0. Counseling about the study and about the 
isotretinoin medication will take place prior to any signing of the study consent 
form. The participant will be asked to repeat back to the provider his or her 
understanding of the study and potential risks/benefits of the medication. The 
consent form for the study will be signed by the participant if the patient agrees 
to enroll in the study after counseling by a Study Coordinator. The participant 
will also enroll in IPLEDGE (isotretinoin monitoring system) with the help of 
the clinician where he or she will sign IPLEDGE consent forms.  
• 
For participants who are not yet adults, parental permission will be obtained to 
enroll the participant with the participant’s blessing. Assent will be obtained 
from all children during enrollment. If the participant turns eighteen during the 
study period, the participant will then provide written consent to continue the 
study; this will occur either in-person at a clinical visit or through electronic 
consent with a study investigator. Cognitively impaired adults are excluded 
from the study population.  
• 
All participants will be reminded at each monthly follow-up visit that they can 
remove themselves from the study at any time. 
10.0 Study Design / Methods 
This will be an open-label, prospective, proof-of-concept study of patients with 
moderate inflammatory acne. The patients will be treated for at least 4 months.  
• The initial acne assessment will be performed by dermatologists and 
dermatology residents using a validated, clinical grading system 
(Comprehensive Acne Severity Scale, CASS as below) with lesion counts 
(inflammatory and noninflammatory). Only moderate acne patients who are 
eligible for enrollment will be allowed to participate. Recruitment methods are 
outlined in above section 8.0. A baseline photo will be taken and placed in the 
patient’s medical chart (Epic). 

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• The participants will be treated with once weekly isotretinoin at a dosage of 1-
1.5mg/kg/week. Exact dosage will be determined by the provider. 
• Efficacy will be determined by having one trained individual (“Photo 
Reviewer”) grade patients’ facial photographs to limit interrater reliability bias. 
This person will not be told what is being used as the study drug, and will not 
be told any details of the study, including that all participants are on the study 
drug, in order to limit observer bias (blinded). Every month, clinical photos will 
be submitted for each patient enrolled in the study. The participants will have 
these photos taken at monthly follow-up visits (monthly follow-up visits are 
standard of care per requirements of IPLEDGE, the medication monitoring 
system for isotretinoin). For in-person visits, these monthly photos will be taken 
by the provider or staff in clinic and directly uploaded to the Epic electronic 
medical record. For any virtual clinic visits (given the COVID-19 pandemic), 
the monthly photos will be submitted into MyChart by the patient.  
• The Study Coordinator (Dermatology research fellow), who per the study 
consent form has permission to access participants’ medical records for the 
purpose of the study, will follow each patient through Epic electronic medical 
record to confirm that photos are submitted in a timely manner. 
• A separately trained individual (“Data Retriever”), who per the study consent 
form has permission to access participants’ medical records for the purpose of 
the study, will submit any uploaded photos (baseline and at the end of each 

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month) from Epic to the Photo Reviewer by secure, encrypted email, labeling 
only with participant number and date of photo. This ensures that the Photo 
Reviewer is always reviewing only individual photos and will not ever enter the 
patient’s medical chart to further limit bias.  
• Photo Reviewer will receive photos and document a monthly CASS grade for 
each participant (in encrypted Excel only accessible by study team members, 
using study participant numbers without patient identifiers, attachment F). 
Baseline photos will all be a grade 3 (moderate) based on study inclusion 
criteria. “Improvement” is defined as decrease in grade from a 3 (moderate) to 
either a 2 (mild), 1 (almost clear), or 0 (clear). “Failure” is defined as showing 
no improvement (remaining a grade 3), increasing grade of 4 (severe) or 5 (very 
severe), or requiring additional oral treatment (for example, worsening acne 
requiring conventional dose isotretinoin). Treatment success can then be 
calculated as the percentage of participants with improvement out of the total 
number of participants at the end of four months, in addition to treatment 
success after each month of treatment. 
• Any participants who take any oral tetracycline antibiotics or trimethoprim-
sulfamethoxazole during the study period (for a reason besides acne) will be 
removed from the study in order to prevent any confounding. Patients requiring 
these medications for acne after the study period has begun will remain 
included in the study and will be listed as intervention “failure” as above. 
Participants will be allowed to continue use of topical acne cleansers and 
treatments during the study as per standard of care.  
• Photo Reviewer will be a blinded medical student because all of the 
dermatology residents will be participating in the clinical care of study 
participants. The Photo Reviewer will be trained by the Primary Investigator 
(Dermatology Resident) and Study Coordinator (Dermatology Research 
Fellow) on how to use the objective CASS grading system.  
• Data Retriever will be a Dermatology resident who will be trained by the 
Primary Investigator (Dermatology Resident) and Study Coordinator 
(Dermatology Research Fellow). 
• All participants, regardless of whether they show “improvement” or “failure,” 
will be followed for up to four months after the study period to assess for 
recurrence of acne. During this period, any further treatment decisions will be 
made by the patient and his or her clinician.  Any participants who choose to 
continue once weekly isotretinoin will be asked to upload clinical photos and 
patient satisfaction surveys monthly through MyChart. Other participants who 
discontinue the isotretinoin will be asked about their follow-up acne treatment. 
To determine patient adverse effects (secondary endpoint), we will monitor for side-
effects of the interventional medication.  
• Per standard of care, patients will be enrolled in IPLEDGE, requiring extensive 
counseling before starting the isotretinoin medication, monthly follow-up visits 
for males and females, and monthly urine pregnancy tests for females.  
• Each patient will fill out a survey at baseline (attachment C) and at each 
monthly visit (attachment G) inquiring about potential side-effects of 
isotretinoin (with severity) including dry skin, dry mucous membranes (lips, 

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eyes), GI upset, bone or muscle pain, night vision abnormalities, mood 
swings/depression, headaches, delayed wound healing.  If the follow-up visit 
between the patient and his or her clinician is virtual, the attached surveys will 
be sent in an encrypted email for completion by the participant. Photos of each 
completed survey will be uploaded into the patient’s chart either at their clinic 
visit or by the patient via MyChart (virtual visit).  
• Per standard of care, laboratory blood work (CBC, CMP, lipid panel) will be 
obtained prior to starting the medication and will be repeated two months into 
the study period (after two clinical follow-up visits, also per standard of care 
and confirmed by PRA), or more frequently if clinically indicated. The results 
will be reviewed from the medical record. 
• Pregnancy test data will be collected from the medical record as these will be 
performed as part of the clinical care of the patient. Female participant’s 
individual providers will order pregnancy tests, which per standard of care are 
typically collected at baseline x 2 (one month apart), every month while on the 
medication, and at least one month after stopping the medication. If patients 
have any significant laboratory abnormalities that could be related to the 
medication, the medication will be discontinued. 
• The Study Coordinator (Dermatology research fellow) will follow each patient 
through Epic electronic medical record to confirm that laboratory work and 
surveys are completed in a timely manner. 
• Data Retriever will follow each participant’s laboratory blood work and any 
abnormalities will be entered into the encrypted Excel sheet; this individual will 
also enter all survey responses into the same encrypted Excel sheet (attachment 
F). 
To determine patient satisfaction (secondary endpoint), the Dermatology Life Quality 
Index (https://www.cardiff.ac.uk/medicine/resources/quality-of-life-
questionnaires/dermatology-life-quality-index) will be administered at baseline before 
receiving any medication and at each monthly follow-up visit. The DLQI is the most 
frequently used validated, patient-reported outcome measure in dermatology trials 
(attachment B). License for use of survey has been obtained (attachment H).  
• Data Retriever will follow each participant’s surveys and enter information into 
the same encrypted Excel sheet as noted above. 
11.0 Specimen Collection and Banking (if applicable) 
• Urinary pregnancy tests (obtained per standard of care per IPLEDGE 
requirements and per the clinical care team) may be collected at each 
participant’s clinic visits in the MUSC outpatient dermatology clinic. For 
virtual follow-up visits, per current standard of care by IPLEDGE during 
COVID-19 pandemic, females can also take a home pregnancy test and label 
with name, date, and time and submit a photo of the test through MyChart 
(Epic). Pregnancy test results will be obtained from the medical record. 
Laboratory blood work will be drawn through either the MUSC lab or through 
LabCorp so that results will be automatically uploaded into the patient’s Epic 
medical chart. No specimens will be collected or kept by investigators.  
12.0 Data Management  

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• 
Participant clinical photos, signed consent form, and photos or scans of their 
completed surveys will be uploaded into the Media tab of Epic electronic health 
record either in clinic or by the patient through MyChart. Laboratory result 
information will result in the patient’s Epic medical chart. This will keep this 
information secure and protected. Study team members will have permission to 
access study participants’ medical records for the purpose of retrieving information 
for the study, as listed in the study consent form. 
• 
Data Retriever will securely email (“send secure”) the participant photos 
(deidentified) to the Photo Reviewer to score. This will occur over MUSC email 
only.  
• 
Storing of synthesized study information (participant follow-up dates, scoring of 
clinical photos, list of any participant lab abnormalities, participant survey answers) 
will be entered in an encrypted Excel sheet, labeled only with participant number and 
without patient identifiers (attachment F). Only investigators directly involved with 
the study will have access to this encrypted Excel sheet. 
• 
Paper consent forms will be stored in a locked office (Rutledge Tower, dermatology 
office floor 10). Electronic consent forms will be stored on a MUSC desktop 
computer that is secured by username and password. Photos of all consent forms will 
be taken for upload into patient’s Media tab in their medical chart. 
• 
Since this is a proof-of-concept study, there will not be any statistical analysis. 
Observations will be reported. 
• 
Data will not leave MUSC. 
13.0 Provisions to Monitor the Data to Ensure the Safety of Subjects (if applicable) 
• Data Retriever (as above), the Principal Investigator, and the Study Coordinator will serve 
as a data monitoring committee. At the end of each month, Data Retriever will review each 
participant’s laboratory blood work results and surveys and input the information into the 
encrypted Excel sheet. This Excel sheet will be reviewed by the rest of the data monitoring 
committee. The clinicians that see each participant will also review laboratory blood work 
as it is completed and are instructed to notify the investigators with any significant 
abnormalities as they arise. Any pertinent abnormalities (elevated liver enzymes, elevated 
triglycerides) will be discussed with the patient by their individual providers and the 
decision to continue or discontinue isotretinoin will be a joint patient-provider decision 
made at that visit based on clinical judgement. Additionally, any clinically significant 
baseline laboratory abnormalities will exclude the patient from enrolling in the study. If the 
patient’s liver enzymes or triglycerides increase to > 3 times the upper limit of normal 
during the study period, the medication will be stopped.  
14.0 Withdrawal of Subjects (if applicable) 
• 
Study investigators may withdraw a participant from the study at any time at their 
discretion. Circumstances can include when a participant’s safety may be 
compromised such as when a participant is experiencing adverse events requiring 
discontinuation of the drug, if the study is stopped in relation to risk to participants, 
or when the participant is non-compliant with the medication regimen.  
• 
A study investigator will inform the participant that he or she has been withdrawn 
from participation and the reasons therefore.  

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• 
At any time, a participant can withdraw from participation in some or all 
components of the study.  
o When the participant withdraws, the participant will no longer 
receive isotretinoin at the experimental regimen.  
o The participant’s medical record or other confidential records will 
not be accessed by the investigator.  
o The data collected to the point of withdrawal will remain part of the 
study records.  
• At a minimum, documentation of the participant’s withdrawal will include the date, 
rationale, and which component the participant is withdrawing. 
• The Primary Investigator will inform the IRB of the number of participants who 
withdrew and the reason for withdrawal. 
15.0 Risks to Subjects 
• 
There is a risk of a loss of confidentiality of personal information as a result of 
participation in this study which will be mitigated at all costs by the study team 
members.  
• 
There is a risk to embryos of females who become pregnant while on isotretinoin. 
The participant will be educated extensively on these risks and enrolled in the 
IPLEDGE program which per standard of care requires two forms of birth control 
for females of child-bearing potential while on isotretinoin, pregnancy tests at 
baseline, pregnancy tests each month while on the medication, and again one month 
after stopping the medication. 
• 
Risks to participants include those that are present when taking isotretinoin at the 
conventional, higher dose. Potential side-effects of isotretinoin include dry skin, dry 
mucous membranes (lips, eyes), GI upset, bone or muscle pain, night vision 
abnormalities, mood swings/depression, headaches, delayed wound healing, and 
laboratory abnormalities (namely hypertriglyceridemia, elevated liver enzymes). 
Frequent monitoring by the patient’s clinician and monthly monitoring by the data 
monitoring committee will take place to minimize risks to participants (detailed in 
section 13.0). These participants will be taking isotretinoin only once weekly, at a 
dose equivalent of what patients usually take once daily; study dose is 1/7 of the 
usual, weekly total dose. Because of this, we have reason to believe that risks will be 
either the same or less than risks while on conventional dose isotretinoin.   
• 
There is a risk of emotional distress when filling out the monthly surveys. If the 
participant admits to feeling depressed thoughts, the participant will be given the 
appropriate resources and a psychiatric referral can be placed if the patient wishes. If 
the patient admits to suicidal or homicidal ideation, inpatient psychiatry will be 
consulted. 
16.0 Potential Benefits to Subjects or Others 
• 
Potential benefit of intervention is improvement in participants’ moderate acne 
vulgaris. There is benefit of minimal dosing, as well as avoidance of long-term 
antibiotics (and of antibiotic resistance).  

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• 
An additional potential benefit is contributing to furthering medical knowledge 
regarding isotretinoin and moderate acne. If participants show a benefit to this 
alternative isotretinoin dosing, further larger and randomized studies can be 
completed. 
• 
Risks are reasonable in relation to the anticipated benefit to participants. Risks to 
participants include those that are present when taking isotretinoin at the 
conventional, higher dose (detailed in section 15.0). These participants will be 
taking isotretinoin only once weekly, at a dose equivalent of what patients usually 
take once daily; study dose is 1/7 of the usual, weekly total dose. Because of this, we 
have reason to believe that risks will be either the same or less than risks while on 
conventional dose isotretinoin.   
17.0 Sharing of Results with Subjects 
• 
Because this is an open-label study, all participants will know what medication they 
are taking and at what dose. 
• 
Information such as standard of care lab results will be returned to the patient once 
of the results are available. Abnormal results will be followed up by the patient’s 
clinician and data monitoring committee.  
• 
Results regarding the participants and overall response to the medication will be 
withheld during the study until the results are analyzed. 
18.0 Drugs or Devices (if applicable)  
• Isotretinoin (study drug) will be prescribed to each participant through Epic electronic 
medical record. The medication will be paid by each patient’s insurance or by self-pay (per 
MUSC Rutledge Tower Pharmacy, this dosing should be covered by most insurance plans 
and is otherwise $10.36 for a 40 mg isotretinoin pill). The participant will directly pick up 
the medication each month from the pharmacy and will store the medication at home in a 
safe, shaded, secure place. The investigators and study team will not handle or store any 
study drug.  
References 
 
All references are noted and listed by number under their respective sections. 
All attachments are noted and listed by letter within the text and highlighted in yellow.