Ignite Creation Date:
2024-05-06 @ 3:41 AM
Last Modification Date:
2024-10-26 @ 11:37 AM
Study NCT ID:
NCT02349854
Status:
COMPLETED
Last Update Posted:
2017-03-27
First Post:
2015-01-26
Brief Title:
Neurobiology of the Scalp in Seborrheic Dermatitis
Sponsor:
Boston University
Organization:
Boston University
Study Overview
Official Title:
Neurobiology of the Scalp in Seborrheic Dermatitis
Status:
COMPLETED
Status Verified Date:
2017-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Seborrheic dermatitis is a common inflammatory skin condition that causes flaky white to yellowish scales to form on oily areas such as the scalp or inside the ear These scales can occur with or without underlying reddened skin In addition to causing psychological distress low self esteem and embarrassment seborrheic dermatitis is associated with scalp pruritus itch Treatment modalities exist to control scalp flaking and itch associated with seborrheic dermatitis although such therapies often lose efficacy over time As seborrheic dermatitis is a chronic life-long condition better treatments are needed The investigators propose to better characterize in subjects with seborrheic dermatitis involving the scalp versus normal scalp controls a the clinical characteristics of the associated itch and b the pattern of nerve innervation to the scalp In this way the investigators hope to get a comprehensive understanding of the factors causing scalp itch with the aim that this information will create new candidates to which treatment modalities can be designed At least 12 up to 20 subjects and similar number of control subjects without disease will have one clinic visit including questionnaires testing of sensation on the scalp and biopsy of the scalp
Detailed Description:
Seborrheic dermatitis SD is a common skin disorder that mainly affects the scalp causing scale itch and red skin Dandruff a subset of SD shows scale and itch in the absence of associated red skin Seborrheic dermatitis can occur on many different body areas including the scalp eyebrows eyelids creases of the nose lips behind the ears in the outer ear and middle of the chest On the scalp SD is commonly associated with pruritus itch Multifactorial theories have been proposed regarding the pathogenesis of SD and these include irritation from a skin-based yeast called malessizia overproduction of sebum by sebaceous glands in the affected skin areas and individual variability Specifically malassezia produce free fatty acids from sebaceous gland-produced triglycerides and these free fatty acids have an irritant ie non-immunologic effect in those patients with a susceptible predisposition Other factors associated with flares of SD include stress fatigue weather extremes infrequent shampoos or skin cleaning use of lotions that contain alcohol skin disorders such as acne obesity neurologic conditions including Parkinsons disease stroke and head injury and HIV infection What role if any such factors play in the etiology of scalp pruritus in patients with SD is not known Furthermore itch is signaled by specific subsets of nerves in the skin and whether pruritus of SD results from alteration of these nerves by the underlying inflammatory state is unknown Moreover pruritus from the skin can be a result of peripheral sensitization where skin-derived signals activate nerves in the skin to send increased nerve signals into the central nervous system Pruritus sensed in the skin can also be a result of altered central-nervous system processing of skin-derived nerve signals such as when skin-derived touch or pain is misperceived as itch by the central nervous system Whether itch in patients with SD is a result of peripheral andor central sensitization is also not unknown Understanding this distinction has therapeutic implications in that itch that is a result of misprocessing by the central nervous system will not be adequately treated in the short term by skin-administered topical therapies
To better understand the etiology of scalp pruritus in subjects with SD we will determine the clinical characteristics of scalp pruritus in subjects with SD compared with normal controls as well as to determine the relationship between scalp pruritus and changes in cutaneous innervation
METHODS
This exploratory and pilot study has only a single planned visit to the outpatient Dermatology clinic in Shapiro center
Subjects who carry the diagnosis of seborrheic dermatitis and scalp itch or controls who dont either internally referred through routine visits to outpatient Dermatology clinics at BMC or externally referred from outside providers or who respond to recruitment techniques will undergo an initial phone screening to review inclusion and exclusion criteria This screening will involve anonymous screening questions without collection of personal health information Subjectscontrols that meet the criteria to be eligible for the study will then be asked if they are willing to come to BMC for the single study visit Those subjectscontrols that then agree to be scheduled will next be told that we are seeking informed consent by phone for the following minimal risk procedures in preparation for the study visit
1 to place a unique patient code identifier on the screening form and
2 if they are willing to stop using any topical scalp treatments for seborrheic dermatitisdandruff as well as c to stop any prn or elective use of prescribed or over-the counter antihistamines for at least 3 weeks before their scheduled visit
d if they are willing not to wash their hair for at least 48 hours prior to the visit
The consent process will include highlighting that the individual can stop the washout at anytime Those subjectscontrols after undergoing informed consent process read to them over the phone that agree to a and b and c above will then be scheduled for a one hour visit at the outpatient Dermatology floor during a non-clinic time
At this visit all subjectscontrols will first undergo the following
1 Visual and non-invasive inspection of the scalp
2 Completion by the patient of a visual analogue scale VAS score to measure degree of scalp pruritus over the past week This VAS form will have no identifiable health information
3 Review of the inclusionexclusion criteria answers they provided over the phone that after informed consent by phone at the time they gave those answers they agreed to allow us to store with a unique subjectcontrol identifying code
The above 3 minimal risk procedures one of which the patients have already provided informed consent for will happen before study visit screening described in detail in Screening Section 200 below and the second informed consent process is performed This order is to respect the patients time If they no longer meet inclusionexclusion criteria based on the above minimal risk screening they will not be eligible for the study and so would then have unnecessarily undergone additional screening as well as an informed consent process
After obtaining written informed consent to participate in the study the following will occur
1 Female subjects of child-bearing potential will take a urine pregnancy test
2 Subjectscontrols will fill-out a questionnaire for pruritus and a questionnaire that contains additional targeted questions related to their scalp itch and hair care practices
3 Investigators will assess scalp to identify involved pruritic sites along EEG lead axis T3-O1 or secondarily along EEG lead axis C3 to Pz EEG testing is a standard non-invasive neurologic test in which scalp electrodes are placed in well-defined and specified positions on the scalp We will not be doing an EEG or using electrodes We are simply using the anatomic landmarks specified for EEG placement to allow uniform selection of scalp areas to test and biopsy
4 Digital photographs of the patients head focusing on the scalp will be taken
5 At the selected scalp site an investigator will perform the following tests for central sensitization at the selected scalp site see below for methods for these tests
Warm heat methods section below explains this procedure to assess it is or is not felt as itch using 3 mm diameter metal probe
Alloknesis brush to itch if possible on scalp with hair
Hyperknesis enhanced sensation of itch to pinprick
Duration of itch elicited by insertion of a cowhage spicule into the scalp if possible on scalp with hair This procedure is described in detail below
6 The investigator will then perform a single scalp biopsy procedure at the site of central sensitization testing according to standard of care practices The 2mm specimen will be placed into formalin for routine paraffin-embedding The 3mm specimen will be placed into a special fixative that optimizes immunohistochemistry on frozen sections to detect antigens expressed by nerves These specimens will be labeled with the subjectscontrols unique identifying code only and without personal health information
This one visit completes the subjectscontrols entire participation in the study No additional visits will be scheduled unless the individual has opted for suture option and removal of these sutures at BMC but the subjectcontrol will be provided the contact information of the investigator in the rare event that the subjectcontrol requires further care as a complication of the biopsy procedure such as bleeding persistent pain infection andor failure to heal
In all biopsies the density and distribution of different subsets of cutaneous nerve fibers will be determined by immunohistochemistry in the frozen-fixed tissue and the presence or absence of histopathologic features of seborrheic dermatitis will be evaluated in the paraffin-embedded tissue Left over tissue from either the frozen andor the paraffin-embedded tissue will be saved in a repository if the individual consents and the storage of these tissues and safeguards are described in detail in the tissue banking section of the BMC approved IRB protocol
Estimated Duration of Enrollment how long will it take to recruit the required sample size One year
Estimated Duration of Entire Study estimated duration from initial IRB approval through data analysis to close of study Two years Sample Size- Total60 patients with scalp itch and seborrheic dermatitis 30
consent andor fully participate in study 20
expected drop outs withdrawal and terminations 5
screened and not enrolled 5 patients without scalp itch and without seborrheic dermatitis 30
consent andor fully participate in study 20
expected drop outs withdrawal and terminations 5
screened and not enrolled 5
Sample Size Justification
Although the proposed study is exploratory in intent and does not require a formal power statement we can nonetheless estimate power for the primary outcome of no central sensitization in patients with seborrheic dermatitis versus controls for the planned sample size of 20 subjects The expected average mean score for a patient with central sensitization is 3 out of 10 and for a control patient 1 out of 10 with a standard deviation of 1 Therefore for there to be no difference between both groups we would expect both groups to have a mean score of 1 with a standard deviation of 1 In this case if there is truly no difference between the control and experimental group ie no central sensitization then 36 total patients 18 per group are required to be 80 sure 40 total patients 20 per group are required to be 85 sure and 44 total patients 22 per group are required to be 90 sure that the 90 two-sided confidence interval will exclude a difference in means of more than 1 We feel that in this instance certainty over 80 will be clinically meaningful and have opted for 40 instead of 36 to better ensure the date achieves at least 80 certainty
For the total number per cohort some number of patients will contact us and undergo anonymous screening questions without collection of personal health information This number is difficult to predict and those patients that do not meet eligibility criteria based on the answers to these anonymous screening questions are not included in either cohort as there is no risk to them again because no personal health information is being collected
Data Analysis
The proposed study design is one in which for each one of the three specific aims described above there is one dependent variable outcome and 1 independent variable 2 independent populations subjects with seborrheic dermatitis and scalp itch and controls without scalp itch or seborrheic dermatitis For non-normal data we intend to use a non-parametric test such as the Mann Whitney or Wilcoxon rank sum test to assess for statistical differences between the medians between these populations In addition we will use non-parametric analysis such as the Spearman correlation to correlate results of the skin testing with results of the immunohistochemical counts of nerves If in fact distributional assumptions are met to allow parameteric analysis we will use a 2 independent sample t-test to assess for statistical differences between the means
To better understand the etiology of scalp pruritus in subjects with SD we will determine the clinical characteristics of scalp pruritus in subjects with SD compared with normal controls as well as to determine the relationship between scalp pruritus and changes in cutaneous innervation
METHODS
This exploratory and pilot study has only a single planned visit to the outpatient Dermatology clinic in Shapiro center
Subjects who carry the diagnosis of seborrheic dermatitis and scalp itch or controls who dont either internally referred through routine visits to outpatient Dermatology clinics at BMC or externally referred from outside providers or who respond to recruitment techniques will undergo an initial phone screening to review inclusion and exclusion criteria This screening will involve anonymous screening questions without collection of personal health information Subjectscontrols that meet the criteria to be eligible for the study will then be asked if they are willing to come to BMC for the single study visit Those subjectscontrols that then agree to be scheduled will next be told that we are seeking informed consent by phone for the following minimal risk procedures in preparation for the study visit
1 to place a unique patient code identifier on the screening form and
2 if they are willing to stop using any topical scalp treatments for seborrheic dermatitisdandruff as well as c to stop any prn or elective use of prescribed or over-the counter antihistamines for at least 3 weeks before their scheduled visit
d if they are willing not to wash their hair for at least 48 hours prior to the visit
The consent process will include highlighting that the individual can stop the washout at anytime Those subjectscontrols after undergoing informed consent process read to them over the phone that agree to a and b and c above will then be scheduled for a one hour visit at the outpatient Dermatology floor during a non-clinic time
At this visit all subjectscontrols will first undergo the following
1 Visual and non-invasive inspection of the scalp
2 Completion by the patient of a visual analogue scale VAS score to measure degree of scalp pruritus over the past week This VAS form will have no identifiable health information
3 Review of the inclusionexclusion criteria answers they provided over the phone that after informed consent by phone at the time they gave those answers they agreed to allow us to store with a unique subjectcontrol identifying code
The above 3 minimal risk procedures one of which the patients have already provided informed consent for will happen before study visit screening described in detail in Screening Section 200 below and the second informed consent process is performed This order is to respect the patients time If they no longer meet inclusionexclusion criteria based on the above minimal risk screening they will not be eligible for the study and so would then have unnecessarily undergone additional screening as well as an informed consent process
After obtaining written informed consent to participate in the study the following will occur
1 Female subjects of child-bearing potential will take a urine pregnancy test
2 Subjectscontrols will fill-out a questionnaire for pruritus and a questionnaire that contains additional targeted questions related to their scalp itch and hair care practices
3 Investigators will assess scalp to identify involved pruritic sites along EEG lead axis T3-O1 or secondarily along EEG lead axis C3 to Pz EEG testing is a standard non-invasive neurologic test in which scalp electrodes are placed in well-defined and specified positions on the scalp We will not be doing an EEG or using electrodes We are simply using the anatomic landmarks specified for EEG placement to allow uniform selection of scalp areas to test and biopsy
4 Digital photographs of the patients head focusing on the scalp will be taken
5 At the selected scalp site an investigator will perform the following tests for central sensitization at the selected scalp site see below for methods for these tests
Warm heat methods section below explains this procedure to assess it is or is not felt as itch using 3 mm diameter metal probe
Alloknesis brush to itch if possible on scalp with hair
Hyperknesis enhanced sensation of itch to pinprick
Duration of itch elicited by insertion of a cowhage spicule into the scalp if possible on scalp with hair This procedure is described in detail below
6 The investigator will then perform a single scalp biopsy procedure at the site of central sensitization testing according to standard of care practices The 2mm specimen will be placed into formalin for routine paraffin-embedding The 3mm specimen will be placed into a special fixative that optimizes immunohistochemistry on frozen sections to detect antigens expressed by nerves These specimens will be labeled with the subjectscontrols unique identifying code only and without personal health information
This one visit completes the subjectscontrols entire participation in the study No additional visits will be scheduled unless the individual has opted for suture option and removal of these sutures at BMC but the subjectcontrol will be provided the contact information of the investigator in the rare event that the subjectcontrol requires further care as a complication of the biopsy procedure such as bleeding persistent pain infection andor failure to heal
In all biopsies the density and distribution of different subsets of cutaneous nerve fibers will be determined by immunohistochemistry in the frozen-fixed tissue and the presence or absence of histopathologic features of seborrheic dermatitis will be evaluated in the paraffin-embedded tissue Left over tissue from either the frozen andor the paraffin-embedded tissue will be saved in a repository if the individual consents and the storage of these tissues and safeguards are described in detail in the tissue banking section of the BMC approved IRB protocol
Estimated Duration of Enrollment how long will it take to recruit the required sample size One year
Estimated Duration of Entire Study estimated duration from initial IRB approval through data analysis to close of study Two years Sample Size- Total60 patients with scalp itch and seborrheic dermatitis 30
consent andor fully participate in study 20
expected drop outs withdrawal and terminations 5
screened and not enrolled 5 patients without scalp itch and without seborrheic dermatitis 30
consent andor fully participate in study 20
expected drop outs withdrawal and terminations 5
screened and not enrolled 5
Sample Size Justification
Although the proposed study is exploratory in intent and does not require a formal power statement we can nonetheless estimate power for the primary outcome of no central sensitization in patients with seborrheic dermatitis versus controls for the planned sample size of 20 subjects The expected average mean score for a patient with central sensitization is 3 out of 10 and for a control patient 1 out of 10 with a standard deviation of 1 Therefore for there to be no difference between both groups we would expect both groups to have a mean score of 1 with a standard deviation of 1 In this case if there is truly no difference between the control and experimental group ie no central sensitization then 36 total patients 18 per group are required to be 80 sure 40 total patients 20 per group are required to be 85 sure and 44 total patients 22 per group are required to be 90 sure that the 90 two-sided confidence interval will exclude a difference in means of more than 1 We feel that in this instance certainty over 80 will be clinically meaningful and have opted for 40 instead of 36 to better ensure the date achieves at least 80 certainty
For the total number per cohort some number of patients will contact us and undergo anonymous screening questions without collection of personal health information This number is difficult to predict and those patients that do not meet eligibility criteria based on the answers to these anonymous screening questions are not included in either cohort as there is no risk to them again because no personal health information is being collected
Data Analysis
The proposed study design is one in which for each one of the three specific aims described above there is one dependent variable outcome and 1 independent variable 2 independent populations subjects with seborrheic dermatitis and scalp itch and controls without scalp itch or seborrheic dermatitis For non-normal data we intend to use a non-parametric test such as the Mann Whitney or Wilcoxon rank sum test to assess for statistical differences between the medians between these populations In addition we will use non-parametric analysis such as the Spearman correlation to correlate results of the skin testing with results of the immunohistochemical counts of nerves If in fact distributional assumptions are met to allow parameteric analysis we will use a 2 independent sample t-test to assess for statistical differences between the means
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None