Clinical trial NCT04409041
Conditions: Lichen Planopilaris Frontal Fibrosing Alopecia
Sponsor: Washington University School of Medicine
Start date: 2019-09-01; Completion date: 2020-12-31
Enrollment: 43 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Oral naltrexone was initially FDA approved to treat opioid use disorder and alcohol dependence at doses from 50-100mg/day. At lower doses of 1-5mg/day, naltrexone has been used off-label with success in treatment of several dermatologic conditions including the scarring hair loss disease lichen planopilaris. A recent case series of four patients with lichen planopilaris and a subtype, frontal fibrosing alopecia, treated with oral low-dose naltrexone at 3mg daily showed reduction of itch, clinical evidence of inflammation of the scalp, and of disease progression. There were no reported adverse events.

Based on the promising evidence, we propose using low-dose naltrexone at a daily dose of 3mg to treat lichen planopilaris and frontal fibrosing alopecia. The patients would be continued on their other medications for these conditions. The study would be open-label, so all participants would receive the low-dose naltrexone. Patients would be seen at 0,3,6 and 12 months to monitor their progress.

Detailed description:

Arms: arm 1: All participants were prescribed low-dose naltrexone at 3mg oral daily.
Interventions: intervention 1: Low-Dose Naltrexone
Intervention descriptions: intervention 1: Based on the promising evidence, we propose using low-dose naltrexone at a daily dose of 3mg to treat lichen planopilaris and frontal fibrosing alopecia. The patients would be continued on their other medications for these conditions. The study would be open-label, so all participants would receive the low-dose naltrexone. Patients would be seen at 0,3,6 and 12 months to monitor their progress.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
 
 
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1 
 
 
 
Oral Low-Dose Naltrexone in the Treatment of Lichen Planopilaris and 
Frontal Fibrosing Alopecia; an uncontrolled open-label prospective study. 
 
 
Principal Investigator:   
Caroline Mann, MD 
NCT01109041 
 
 
 
 
 
 
Version Date/Number:  
VERSION 1, 8/7/2019 
 


 
 
 
 
 
 
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2 
 
TABLE OF CONTENTS 
 
A 
INTRODUCTION ............................................................................................................................... 4 
A1 
STUDY ABSTRACT ......................................................................................................................... 4 
A2 
PRIMARY HYPOTHESIS ................................................................................................................... 4 
A3 
PURPOSE OF THE STUDY PROTOCOL .............................................................................................. 4 
B 
BACKGROUND .................................................................................................................................. 4 
B1 
PRIOR LITERATURE AND STUDIES .................................................................................................. 4 
B2 
RATIONALE FOR THIS STUDY ......................................................................................................... 5 
C 
STUDY OBJECTIVES........................................................................................................................ 5 
C1 
PRIMARY AIM ................................................................................................................................ 6 
C2 
SECONDARY AIM ....................................................................ERROR! BOOKMARK NOT DEFINED. 
C3 
RATIONALE FOR THE SELECTION OF OUTCOME MEASURES ........................................................... 6 
D 
INVESTIGATIONAL AGENT .......................................................................................................... 6 
D1 
PRECLINICAL DATA ....................................................................................................................... 6 
D2 
CLINICAL DATA TO DATE .............................................................................................................. 6 
D3 
DOSE RATIONALE AND RISK/BENEFITS ......................................................................................... 6 
E 
STUDY DESIGN ................................................................................................................................. 6 
E1 
OVERVIEW OR DESIGN SUMMARY ................................................................................................. 6 
E2 
SUBJECT SELECTION AND WITHDRAWAL....................................................................................... 6 
2.a 
Inclusion Criteria ..................................................................................................................... 6 
2.a 
Exclusion Criteria ..................................................................................................................... 6 
2.b 
Ethical Considerations ............................................................................................................. 7 
2.c 
Subject Recruitment Plans and Consent Process ..................................................................... 7 
2.d 
Randomization Method and Blinding ....................................................................................... 7 
2.e 
Risks and Benefits ..................................................................................................................... 7 
2.f 
Early Withdrawal of Subjects ................................................................................................... 8 
2.g 
When and How to Withdraw Subjects ....................................................................................... 8 
2.h 
Data Collection and Follow-up for Withdrawn Subjects .......................................................... 8 
E3 
STUDY DRUG ................................................................................................................................. 8 
3.a 
Description ............................................................................................................................... 8 
3.b 
Treatment Regimen ................................................................................................................... 8 
3.c 
Method for Assigning Subjects to Treatment Groups ............................................................... 8 
3.d 
Preparation and Administration of Study Drug ........................................................................ 8 
3.e 
Subject Compliance Monitoring ............................................................................................... 8 
3.f 
Prior and Concomitant Therapy ............................................................................................... 8 
3.g 
Packaging ................................................................................................................................. 9 
3.h 
Blinding of Study Drug ............................................................................................................. 9 
3.i 
Receiving, Storage, Dispensing and Return .............................. Error! Bookmark not defined. 
F 
STUDY PROCEDURES ..................................................................................................................... 9 
F1 
SCREENING FOR ELIGIBILITY ......................................................................................................... 9 
F2 
SCHEDULE OF MEASUREMENTS ..................................................................................................... 9 
F3 
VISIT 1 ........................................................................................................................................... 9 


 
 
 
 
 
 
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3 
F4 
VISIT 2 ETC. ............................................................................ERROR! BOOKMARK NOT DEFINED. 
F5 
SAFETY AND ADVERSE EVENTS ..................................................................................................... 9 
5.a 
Safety and Compliance Monitoring ........................................... Error! Bookmark not defined. 
5.b 
Medical Monitoring ................................................................... Error! Bookmark not defined. 
i 
Investigator only ...................................................................................... Error! Bookmark not defined. 
ii 
Independent expert to monitor ................................................................. Error! Bookmark not defined. 
iii 
Institutional Data and Safety Monitoring Board ...................................... Error! Bookmark not defined. 
iv 
Independent Data and Safety Monitoring Board ...................................... Error! Bookmark not defined. 
5.c 
Definitions of Adverse Events ................................................................................................... 9 
5.d 
Classification of Events ............................................................. Error! Bookmark not defined. 
i 
Relationship ............................................................................................. Error! Bookmark not defined. 
ii 
Severity .................................................................................................... Error! Bookmark not defined. 
iii 
Expectedness ........................................................................................... Error! Bookmark not defined. 
5.e 
Data Collection Procedures for Adverse Events .....................................................................10 
5.f 
Reporting Procedures ..............................................................................................................10 
5.g 
Adverse Event Reporting Period ..............................................................................................10 
5.h 
Post-study Adverse Event ........................................................................................................10 
F6 
STUDY OUTCOME MEASUREMENTS AND ASCERTAINMENT ....ERROR! BOOKMARK NOT DEFINED. 
G 
STATISTICAL PLAN ........................................................................................................................10 
G1 
SAMPLE SIZE DETERMINATION AND POWER ...........................ERROR! BOOKMARK NOT DEFINED. 
G2 
INTERIM MONITORING AND EARLY STOPPING ........................ERROR! BOOKMARK NOT DEFINED. 
G3 
ANALYSIS PLAN......................................................................ERROR! BOOKMARK NOT DEFINED. 
G4 
STATISTICAL METHODS ..........................................................ERROR! BOOKMARK NOT DEFINED. 
G5 
MISSING OUTCOME DATA ......................................................ERROR! BOOKMARK NOT DEFINED. 
G6 
UNBLINDING PROCEDURES .....................................................ERROR! BOOKMARK NOT DEFINED. 
H 
DATA HANDLING AND RECORD KEEPING .............................................................................11 
H1 
CONFIDENTIALITY AND SECURITY ................................................................................................11 
H2 
TRAINING................................................................................ERROR! BOOKMARK NOT DEFINED. 
H3 
CASE REPORT FORMS AND SOURCE DOCUMENTS ...................ERROR! BOOKMARK NOT DEFINED. 
H4 
RECORDS RETENTION .............................................................ERROR! BOOKMARK NOT DEFINED. 
H5 
PERFORMANCE MONITORING .................................................ERROR! BOOKMARK NOT DEFINED. 
I 
STUDY MONITORING, AUDITING, AND INSPECTING ..........................................................11 
I1 
STUDY MONITORING PLAN ...............................................................................................................11 
I2 
AUDITING AND INSPECTING ..............................................................................................................11 
J 
STUDY ADMINISTRATION ...........................................................................................................11 
J1 
ORGANIZATION AND PARTICIPATING CENTERS .................................................................................11 
J2 
FUNDING SOURCE AND CONFLICTS OF INTEREST ..............................................................................11 
J3 
COMMITTEES ...............................................................................ERROR! BOOKMARK NOT DEFINED. 
J4 
SUBJECT STIPENDS OR PAYMENTS ..............................................ERROR! BOOKMARK NOT DEFINED. 
J5 
STUDY TIMETABLE .....................................................................ERROR! BOOKMARK NOT DEFINED. 
K 
PUBLICATION PLAN ......................................................................................................................12 
L 
ATTACHMENTS ...............................................................................................................................12 
L1 
TABLES .........................................................................................................................................12 
L2 
INFORMED CONSENT DOCUMENTS.................................................................................................12 
L3 
PATIENT EDUCATION BROCHURES...........................................ERROR! BOOKMARK NOT DEFINED. 
L4 
SPECIAL PROCEDURES PROTOCOLS .........................................ERROR! BOOKMARK NOT DEFINED. 
L5 
QUESTIONNAIRES OR SURVEYS ...............................................ERROR! BOOKMARK NOT DEFINED. 
M 
REFERENCES ...................................................................................................................................12 
 


 
 
 
 
 
 
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4 
A Introduction 
 
A1 Study Abstract 
Oral naltrexone was initially FDA approved to treat opioid use disorder and alcohol 
dependence at doses from 50-100mg/day. At lower doses of 1-5mg/day, naltrexone has 
been used off-label with success in treatment of several dermatologic conditions 
including the scarring alopecia (irreversible hair loss), lichen planopilaris. A recent case 
series of four patients with lichen planopilaris and a subtype, frontal fibrosing alopecia, 
treated with oral low-dose naltrexone at 3mg daily showed reduction of itch, clinical 
evidence of inflammation of the scalp, and of disease progression. There were no 
reported adverse events.  
 
Based on the promising evidence, we propose using low-dose naltrexone at a daily dose 
of 3mg to treat lichen planopilaris and frontal fibrosing alopecia. The patients would be 
continued on their other medications for these conditions. The study would be open-
label, so all participants would receive the low-dose naltrexone. Patients would be seen 
at monthly intervals over a period of six months to monitor their progress. 
 
A2 Primary Hypothesis 
Does daily oral low-dose naltrexone (3mg per day) reduce symptoms and disease 
progression in patients with lichen planopilaris and frontal fibrosing alopecia? 
 
A3 Purpose of the Study Protocol 
To outline background and procedures relating to this study.  
 
B Background 
 
B1 Prior Literature and Studies 
Mechanism 
Naltrexone is an opioid antagonist with multiple systemic pathway effects, including 
those involved in pruritus, wound healing, and immune system homeostasis.1 Low-dose 
oral naltrexone (doses 1-5mg daily) exhibits partial binding to μ, κ, and δ opioid 
receptors, which induces a paradoxical increase in opioid receptor expression as well as 
of endogenous opioids, β-endorphins, and methione-enkephalin.1, 2 In addition to effects 
on the opioid receptors, naltrexone also acts as an antagonist on Toll-like receptor 4, 
thereby producing anti-inflammatory effects through reduction of tumor necrosis factor-α, 
interleukin-6, and nitric oxide.2 The effectiveness of naltrexone is attributed to the 
widespread distribution of opioids and their receptors in the cutaneous neuroendocrine 
system.1 
 
Background 


 
 
 
 
 
 
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5 
Lichen planopilaris (LPP) is an inflammatory, cicatricial alopecia, of which frontal 
fibrosing alopecia is considered a clinical variant.3, 4 Clinical features of LPP include 
perifollicular erythema and scaling leading to destruction of follicular ostia and patchy 
scarring alopecia. In the frontal fibrosing alopecia variant, hair loss occurs on the 
frontotermporal region, often with associated eyebrow loss. Symptoms include pruritus, 
burning, pain, and tenderness. Treatment options are limited and yield inconsistent 
results.3 High potency topical steroids and topical tacrolimus are recommended as first 
line therapies for primary cicatricial alopecias.3 However, topical corticosteroids may be 
less effective in FFA.5 Other frequently utilized treatments include intralesional 
triamcinolone acetonide and topical minoxidil.3 Hydroxychloroquine6 and doxycycline are 
often used as systemic treatments in both LPP and FFA, whereas finasteride/dutasteride 
have been reported successfully in FFA.3, 7 Overall, the level of evidence for the above 
treatments is limited to level IV or V evidence, and further studies into this scarring 
disease are needed.8 
 
Oral naltrexone is FDA approved to treat opioid dependence and alcohol use disorder at 
doses from 50-100mg/day. At lower doses of 1-5mg/day, naltrexone has been used off-
label with success in treatment of several dermatologic conditions including lichen 
planopilaris. A recent case series of four patients with lichen planopilaris and a subtype, 
frontal fibrosing alopecia, treated with oral low-dose naltrexone at 3mg daily showed 
reduction of pruritus, clinical evidence of scalp inflammation, and of disease 
progression.3 
 
While initial studies using LDN for dermatologic conditions is promising, the level of 
evidence is low, generally limited to case reports and series. Recently, three excellent 
summaries of evidence for naltrexone in dermatologic conditions have been published.1, 2, 9 
A recent review article of therapy for FFA includes naltrexone at 3 mg/day in their FFA 
treatment algorithm.7  
 
LDN maintain stability and efficacy through 90 days when crushed into water. One method 
of dosing is to crush ten 50mg tablets of naltrexone (500mg total) into 500 mL of water or 
juice, thus creating a 1mg/mL solution. This can be shaken prior to dispensing. At the time 
of reporting, this solution cost about $15.10 
 
B2 Rationale for this Study 
While initial studies using LDN for dermatologic conditions is promising, the level of 
evidence is low, generally limited to case reports and series. Based on case reports, we 
expect the participant to benefit though decrease in their symptoms (burning, itching) as 
well as decreased redness and scale and possibly slowing or halting disease 
progression.  
This increased data would benefit society by providing further evidence for the use of 
low-dose naltrexone in lichen planopilaris and frontal fibrosing alopecia. 
 
 
C Study Objectives 
 


 
 
 
 
 
 
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6 
C1 Primary Aim 
Based on case reports, we expect the participant to benefit though decrease in their 
symptoms (burning, itching) as well as decreased redness and scale and possibly 
slowing or halting disease progression.  
 
C2 Rationale for the Selection of Outcome Measures 
A recent case series of four patients with lichen planopilaris and a subtype, frontal 
fibrosing alopecia, treated with oral low-dose naltrexone at 3mg daily showed reduction 
of pruritus, clinical evidence of scalp inflammation, and of disease progression.3 
 
 
D Investigational Agent  
 
D1 Preclinical Data 
D2 Clinical Data to Date  
D3 Dose Rationale and Risk/Benefits  
See section B above.  
 
E Study Design  
 
E1 Overview or Design Summary 
Uncontrolled open-label prospective study 
 
E2 Subject Selection and Withdrawal  
 
2.a 
Inclusion Criteria  
Adults age 18 or greater with clinically or histologically confirmed diagnosis of lichen 
planopilaris or frontal fibrosing alopecia are eligible. 
2.a 
Exclusion Criteria  
Patients with known allergy or hypersensitivity to naltrexone will be excluded. Patients 
will be screened for opioid use with urine screen for opioids, and any patients with 
positive test or concurrent use of opioids will be excluded from the study. Postmarketing 
reports of suicidal thoughts, attempted suicide and depression have been reported with 
high dose naltrexone. While no reports of mood changes have been reported with low-
dose naltrexone, patients will be counseled to report any mood changes that arise during 


 
 
 
 
 
 
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7 
their treatment.  Patients with currently active depression, schizophrenia, and bipolar 
disorder will be excluded.  
 
 
2.b 
Ethical Considerations  
Eligeable subjects may take naltrexone without enrolling in the study to eliminate 
coercion.  
 
2.c 
Subject Recruitment Plans and Consent Process 
Patients will be recruited from the pool of patients seen at Washington University/BJH 
dermatology clinics with existing and new diagnoses of lichen planopilaris and frontal 
fibrosing alopecia. Recruitment will be by word of mouth. Participants will be adequately 
informed about the study and have an opportunity to ask questions prior to enrollment. 
They will be seen during routine dermatology clinic visits and evaluated per protocol to 
determine eligibility for the study. Patients will have an opportunity to read and take 
home the consent form. Enrollment will be on a rolling basis between September 1st and 
October 31st, 2019. Patients who enroll in the study will be followed in Dr. Caroline 
Mann’s dermatology clinic at 969 North Mason Road (BJH West County). We will 
confirm with patients that they have decision-making capacity and the ability to 
understand the risks and benefits of the treatment.  
 
Patients who do not respond to the invitation to participate in the study will be contacted 
at the phone number in their medical record to address any questions they may have 
and to confirm whether or not they will participate. Opt-out procedures include verbally 
indicating that they do not wish to participate.  
 
Study participants will receive a copy of the consent document for their records. 
Participants will be given a signed copy of the consent document. This will be provided 
to them at the time of signing. The form will also be scanned into their electronic medical 
record.  
 
2.d 
Randomization Method and Blinding 
N/A, not randomized  
2.e 
Risks and Benefits 
Based on case reports, we expect the participant to benefit though decrease in their 
symptoms (burning, itching) as well as decreased redness and scale and possibly 
slowing or halting disease progression.  
This increased data would benefit society by providing further evidence for the use of 
low-dose naltrexone in lichen planopilaris and frontal fibrosing alopecia. 
 
Use of naltrexone in patients on long-term opioids may induce opioid withdrawal, so 
patients will be screened for opioid use. Additionally, as LDN upregulates the number of 
opioid receptors, patients must be cautioned that this can potentiate the effect of opioid 
agonists, leading to risk of opioid overdose.1 Patients will be advised that if they require 
emergent pain control for other conditions, opioid alternatives should be considered or if 


 
 
 
 
 
 
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8 
opioids are required, they are administered under the direct supervision of a physician. 
While long-term safety data are not available, side effects with low-dose naltrexone are 
minimal, not significantly different from placebo, and include vivid dreams, nightmares, 
and headaches.1 Morning dosing of low-dose naltrexone can decrease these effects, if 
present.2 Based on studies involving retrospective chart reviews of patients treated with 
LDN for multiple sclerosis and Crohn’s disease without significant laboratory 
abnormality, Lee and Elston concluded that no laboratory testing is required in the 
absence of specific signs or symptoms.2  Postmarketing reports of suicidal thoughts, 
attempted suicide and depression have been reported with high dose naltrexone. While 
no reports of mood changes have been reported with low-dose naltrexone, patients will 
be counseled to report any mood changes that arise during their treatment. 
 
2.f 
Early Withdrawal of Subjects  
Subjects may withdraw by telling the study team they are no longer interested in 
participating in the study or by sending a withdrawl letter. The investigator may also 
decide to end participation due to patient becoming ineligeable (see eligibility criteria 
above) or due to unforeseen safety issues.  
2.g 
When and How to Withdraw Subjects  
Subjects will be contacted be phone or in person at a routine office visit. 
2.h 
Data Collection and Follow-up for Withdrawn Subjects  
All data obtained prior to withdrawal will be included in the data analysis.  
 
E3 Study Drug  
 
3.a 
Description  
Naltrexone 
3.b 
Treatment Regimen  
Low dose naltrexone at 3mg PO daily.  
3.c 
Method for Assigning Subjects to Treatment Groups  
N/A: open-label, non-randomized, uncontrolled study 
3.d 
Preparation and Administration of Study Drug  
Will be compounded by a compounding pharmacy. 
3.e 
Subject Compliance Monitoring  
Will be reviewed at regular follow-up visits at 0,3,6 and 12 months.  
3.f 
Prior and Concomitant Therapy  
Low-dose naltrexone, 3mg orally to be taken daily, will be prescribed. They will be 
continued on their other treatment medications for lichen planopilaris (LPP) and frontal 


 
 
 
 
 
 
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9 
fibrosing alopecia (FFA) during the study period without increasing dose. During the 
study period, other LPP and FFA medications may be decreased in dose or 
discontinued, but will not be increased or added. This will allow the investigators to 
analyze the specific benefit of naltrexone. 
 
3.g 
Packaging  
As per compounding pharmacy.  
3.h 
Blinding of Study Drug  
N/A 
 
F Study Procedures  
 
F1 Screening for Eligibility 
This will be performed at a routine office visit prior to enrolling in the study. 
 
F2 Schedule of Measurements 
Performed at 0,3,6, and 12 month office visits.  
 
F3 Visits 
At each office visit, data will be collected as outlined on the patient assessment form. We 
will confirm with patients that they are not taking opioids medications and that their mood 
is stable without evidence of depression. Additionally, patients will be asked about any 
adverse reactions that they might notice from the medication, specifically inquiring about 
vivid dreams, nightmares, and headaches, as well as any other side effects they have 
noticed with the medication. The study will begin between September 1st and October 
31st 2019 and continue until December 31st 2020. 
F4 Safety and Adverse Events  
Patients will be screened at each office visit. In addition, they will be encouraged to 
report any concerns or issues to Dr. Caroline Mann at the contact information listed on 
the consent form.  
 
 
4.a 
Definitions of Adverse Events 
 
Reported adverse events with low-dose naltrexone are rare and mild. Vivid dreams, 
nightmares, and headaches have been reported with low-dose naltrexone used for other 
conditions. A recent case series of four patients with lichen planopilaris and a subtype, 
frontal fibrosing alopecia, treated with oral low-dose naltrexone at 3mg daily showed 


 
 
 
 
 
 
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10
reduction of itch, clinical evidence of inflammation of the scalp, and of disease 
progression. There were no reported adverse events.  
 
4.b 
Data Collection Procedures for Adverse Events 
All adverse events will be recorded in the patient’s medical record as well as on a secure 
document (Excel spreadsheet in Wustl Box) and will be reviewed monthly by the study 
team.  
4.c 
Reporting Procedures 
Subjects may report in person or by telephone at any time during the study.  
4.d 
Adverse Event Reporting Period 
September 1st 2019 and December 31st, 2020 
4.e 
Post-study Adverse Event 
Patients may report post-study adverse to Dr. Caroline Mann at any time after the study 
is completed.  
 
G Statistical Plan  
 
Longitudinal data from time points at 0,3,6 and 12 months will be analyzed for each 
component of the data collection form, including components of the patient assessment 
of itch and burning/pain (each on a 0-10 point scale), physician assessment for 
erythema and scale (each on a 0-3 scale) as well as longitudinal comparisons of 
measurement of the scalp involvement (distance in cm from the glabella to hairline in 
FFA, and area of scarring/redness/scaling in cm2 for LPP). See below for data collection 
form. 
 
We predict that oral low-dose naltrexone would lead to approximately 2-3 point decrease 
in each of the 0-10 point patient assessments (itch and burning/pain) and a 1-2 point 
decrease in each of the 0-3 point physician assessments (erythema and scale). We 
expect the areas of scalp involvement to remain stable over the analysis period. 
 
Patient characteristics will be summarized using descriptive statistics. The longitudinal 
outcomes will be analyzed using mixed model analysis to account for the correlation of 
measures from the same subject. Time effect will be assessed and contrasts will be 
used to compare mean difference between any two time points of interest. All statistical 
tests will be two-sided with a significance level of 0.05 and performed with SAS 9.4. 
Careful attention will be paid to ensuring that data satisfy assumptions required of a 
particular analytic strategy. When required assumptions are violated, we will explore the 
use of data transformations and potentially, perform some analyses using non-
parametric or semi-parametric methods based on the rank of some variables. 
 
Data on the quantitative effect size of naltrexone for LPP/FFA is limited, but based on 
clinical experience and descriptive case studies, we would expect patients to start at a 4-
5/10 on the itch/pain/burning scales, and predict that it could decrease to 1-2/10 with 


 
 
 
 
 
 
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11
naltrexone treatment. Similarly, we expect that patients would start at a 1-2/3 on the 
physician assessments (erythema and scale) and predict that the physician 
assessments of erythema and scale could decrease to a 0-1/3. Finally, we expect the 
areas of scalp involvement to remain stable over the analysis period. Based on existing 
data showing low number of mild side effects and no serious adverse events, we plan to 
enroll 75-100 patients, which is the maximum number that we would expect to see over 
the study period given the low prevalence of disease. 
 
With estimated standard deviation using a rule of thumb based on range of the scales, 
the anticipated 75-100 patients can achieve at least 80% power to detect mean 
difference of 0.7-0.8 based on patient assessment as well as 0.21-0.25 based on 
physician assessment. Therefore, the anticipated sample size is sufficient to detect the 
expected effects. The power was based on two-sided paired t-test comparing before and 
after treatment at significance level 0.05. 
 
H Data Handling and Record Keeping  
 
H1 Confidentiality and Security 
Data will be kept in the patient’s medical record or in secure files in Wustl Box. Persons 
that have access to the medical record will be able to view data. Only the investigators of 
this study will have access to the secure files in Wustl Box.  
 
 
I Study Monitoring, Auditing, and Inspecting  
 
I1 
Study Monitoring Plan  
None.  
I2 
Auditing and Inspecting  
None.  
J Study Administration 
 
J1 Organization and Participating Centers 
Washington University in St. Louis.  
J2 Funding Source and Conflicts of Interest 
Funding from the WashU division of Dermatology. No conflicts of interest.  
 
 


 
 
 
 
 
 
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K Publication Plan  
 
 
Plan to submit for publication in Spring 2020.  
 
L  Attachments  
 
L1  Tables  
Data collection sheet.  
L2  Informed consent documents 
 
The above are attached as part of the IRB.  
 
M References 
 
1. Ekelem C, Juhasz M, Khera P , Mesinkovska NA. Utility of Naltrexone Treatment for 
Chronic Inflammatory Dermatologic Conditions: A Systematic Review. JAMA 
dermatology 2018. 
2. Lee B , Elston DM. The uses of naltrexone in dermatologic conditions. J Am Acad 
Dermatol 2019;80:1746-52. 
3. Strazzulla LC, Avila L, Lo Sicco K , Shapiro J. Novel Treatment Using Low-Dose 
Naltrexone for Lichen Planopilaris. Journal of drugs in dermatology : JDD 2017;16:1140-
2. 
4. Bolduc C, Sperling LC , Shapiro J. Primary cicatricial alopecia: Lymphocytic primary 
cicatricial alopecias, including chronic cutaneous lupus erythematosus, lichen 
planopilaris, frontal fibrosing alopecia, and Graham-Little syndrome. J Am Acad 
Dermatol 2016;75:1081-99. 
5. Racz E, Gho C, Moorman PW, Noordhoek Hegt V , Neumann HA. Treatment of 
frontal fibrosing alopecia and lichen planopilaris: a systematic review. J Eur Acad 
Dermatol Venereol 2013;27:1461-70. 
6. Chiang C, Sah D, Cho BK, Ochoa BE , Price VH. Hydroxychloroquine and lichen 
planopilaris: efficacy and introduction of Lichen Planopilaris Activity Index scoring 
system. J Am Acad Dermatol 2010;62:387-92. 
7. Ho A , Shapiro J. Medical therapy for frontal fibrosing alopecia: A review and clinical 
approach. J Am Acad Dermatol 2019. 
8. Sperling LC , Nguyen JV. Commentary: treatment of lichen planopilaris: some 
progress, but a long way to go. J Am Acad Dermatol 2010;62:398-401. 
9. Jaros J , Lio P. Low Dose Naltrexone in Dermatology. Journal of drugs in dermatology 
: JDD 2019;18:235-8. 
10. Bronfenbrener R. Inexpensive compounding of low dose naltrexone (LDN) with 
orange juice. J Am Acad Dermatol 2019. 
 
 


 
 
 
 
 
 
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