Androgenetic AlopeciaNCT03694067
Androgenetic Alopecia and the JAK-STAT Pathway
An observational study of Androgenetic Alopecia, run by Cairo University at 1 site in Egypt.
Trial summary
It is a well known fact that the JAK-STAT pathway plays a pivotal role in the pathogenesis of alopecia areata. Both phosphorylated STAT 1 and 3 have been found to be upregulated in the disease. However, whether this pathway plays a role in other hair loss disorders remains unclear. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Androgenetic Alopecia
- What is being tested?
- Punch skin biopsy
- How many people
- 25 participants
- Where
- 1 siteEgypt
- Study dates
- 15 Oct 2018to 1 Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Study population: Specialized dermatology clinic at Cairo University
Who may be able to join
- Males with androgenetic alopecia not receiving topical treatment nor systemic treatment for hair loss for at least 6 month prior to the study
Who cannot join
- Patients with localized or generalized hair loss due to causes other than androgenetic alopecia.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Assessment of the Role of the JAK-STAT Pathway in the Pathogenesis of Male Androgenetic Alopecia
It is a well known fact that the JAK-STAT pathway plays a pivotal role in the pathogenesis of alopecia areata. Both phosphorylated STAT 1 and 3 have been found to be upregulated in the disease. However, whether this pathway plays a role in other hair loss disorders remains unclear. The study aims at assessing STAT3 levels in male patients with androgenetic alopecia. The investigators hypothesize that STAT3 levels will be elevated (due to a previous study proving that JAK-STAT pathway is involved in non-immune mediated hair loss in mice.
Read the detailed description
Background and rationale Androgenetic alopecia occurs in men and women,and is characterised by the loss of hair from the scalp in a defined pattern. Determining factors appear to be genetic predisposition coupled with the presence of sufficient circulating androgen.
The transformation of testosterone into dihydrotestosterone(DHT) by type 2 5-alpha reductase, which causes hair miniaturization,is universally accepted as the main player in the disease's pathogenesis. Nonetheless,how DHT causes hair thinning is not well understood. New studies revealed that a lymphocytic microfolliculitis targeting the bulge epithelium along with deposits of epithelial basement membrane zone immunoreactants are frequent findings in androgenetic alopecia and could point toward an immunologically driven trigger.
Tyrosine kinases (TKs) are enzymes involved in intracellular signaling that catalyze the phosphorylation of tyrosine residues on protein substrates. They are key components of signaling pathways that drive any array of cellular responses including proliferation, differentiation, migration and survival. Janus kinases (JAKs) are specific TKs.
Signal transducer and activator of transcription (STAT) proteins are transcription factorsprimarily phosphorylated and activated by JAKs.The JAK-STAT pathway is utilized by cytokines including interleukins (ILs), interferons (IFNs), and other molecules to transmit signals from the cell membrane to the nucleus. Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis and vitiligo.
It is a well known fact that the JAK-STAT pathway plays a pivotal role in the pathogenesis of alopecia areata. Both phosphorylated STAT 1 and 3 have been found to be upregulated in the disease. However, whether this pathway plays a role in other hair loss disorders remains unclear. A study showedthat topical treatment of mouse and human skin with small molecule inhibitors of the JAK-STATpathway resulted in rapid onset of anagen and subsequent hair growth. It was shown that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ. These findings indicate that the JAK-STAT pathway may be involved, not only in immune-mediated hair loss (alopecia areata), but also in the normal hair cycle.
This current study aims at assessing STAT3 levels in patients with androgenetic alopecia, in an attempt to detect a possible role of the JAK-STAT pathway in the pathogenesis of the disease.
Objective:
The objective is to compare tissue levels of STAT3 in androgen-dependant areas in male androgenetic alopecia patients with their level in non-involved, non-androgen dependant areas (occipital scalp) in the same subjects.
Population of study \& disease condition (e.g women with hepatitis, ............) Males with androgenetic alopecia
Background and demographic characteristics( e.g age,.......)
- Age above 18 years.
- Males
Interventions :
Each subject will be subjected to:
- Informed consent.
- Detailed history and clinical evaluation to determine severity of disease.
- Punch biopsies (1mm) of affected area of scalp (androgen dependent area) from 25 patients with androgenetic alopecia.
- Punch biopsies(1mm) of normal area of scalp from occipital scalp (non-androgen dependent area) from the same 25 patients
- Quantification of STAT3 by polymerase chain reaction (PCR).
Sample size (number of participants included)
- 25 participants (That will serve as both patients and controls)
- Sample size calculation was done using G ⃰ Power 3.1.9.2.
Possible. Risk Bleeding, secondary infection, scarring.
- Conditions
- Androgenetic Alopecia
- Being tested
- Punch skin biopsy
- Keywords
- Androgenetic, Alopecia, JAK, STAT
- Medical subject headings
- Alopecia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Punch skin biopsyOther
One 1 mm punch biopsy will be taken from the patients from balding scalp. Another 1 mm punch biopsy will be taken from an area of occipital non-balding scalp of the same individual. Local anesthesia will be injected around the biopsy site beforehand.
| Study group | Role | What they receive |
|---|---|---|
| Androgenetic alopecia patients | Two 1 mm scalp punch skin biopsy will be taken per patient Receives: Other: Punch skin biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Different in STAT3
STAT3 levels in androgen-dependant areas compared to non-involved areas from occipital scalp(in an attempt to assess the possible role of the JAK-STAT pathway in androgenetic alopecia).
Measured: 6 months
Secondary outcomes (1)
Correlating STAT3 with severity
The relation of STAT3 levels to the severity of androgenetic alopecia (Hamilton-Norwood scale)
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2018
- Study start15 Oct 2018
- Primary completion1 Dec 2019
- Study completion1 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Androgenetic AlopeciaStudies of the same condition, open and under way.
- More trials run by Cairo UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aya AlOrbani, Cairo University
- Investigators
- Akmal S Hassan, MD, Study director, Cairo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03694067
- Sponsor's protocol ID
- Atm567
- Status last verified
- Jan 2020
- First submitted
- 1 Oct 2018
- Last updated
- 28 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Damsky W, King BA. JAK inhibitors in dermatology: The promise of a new drug class. J Am Acad Dermatol. 2017 Apr;76(4):736-744. doi: 10.1016/j.jaad.2016.12.005. Epub 2017 Jan 28.
PubMed 28139263Ellis JA, Sinclair R, Harrap SB. Androgenetic alopecia: pathogenesis and potential for therapy. Expert Rev Mol Med. 2002 Nov 19;4(22):1-11. doi: 10.1017/S1462399402005112.
PubMed 14585162Harel S, Higgins CA, Cerise JE, Dai Z, Chen JC, Clynes R, Christiano AM. Pharmacologic inhibition of JAK-STAT signaling promotes hair growth. Sci Adv. 2015 Oct 23;1(9):e1500973. doi: 10.1126/sciadv.1500973. eCollection 2015 Oct.
PubMed 26601320Magro CM, Rossi A, Poe J, Manhas-Bhutani S, Sadick N. The role of inflammation and immunity in the pathogenesis of androgenetic alopecia. J Drugs Dermatol. 2011 Dec;10(12):1404-11.
PubMed 22134564O'Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A. The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med. 2015;66:311-28. doi: 10.1146/annurev-med-051113-024537.
PubMed 25587654Paniagua RT, Fiorentino DF, Chung L, Robinson WH. Tyrosine kinases in inflammatory dermatologic disease. J Am Acad Dermatol. 2011 Aug;65(2):389-403. doi: 10.1016/j.jaad.2010.04.026. Epub 2010 Jun 26.
PubMed 20584561Schwartz DM, Bonelli M, Gadina M, O'Shea JJ. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat Rev Rheumatol. 2016 Jan;12(1):25-36. doi: 10.1038/nrrheum.2015.167. Epub 2015 Dec 3.
PubMed 26633291Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci. 2004 Mar 15;117(Pt 8):1281-3. doi: 10.1242/jcs.00963. No abstract available.
PubMed 15020666Whiting DA. Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss. J Am Acad Dermatol. 2001 Sep;45(3 Suppl):S81-6. doi: 10.1067/mjd.2001.117428.
PubMed 11511857Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, de Jong A, Harel S, DeStefano GM, Rothman L, Singh P, Petukhova L, Mackay-Wiggan J, Christiano AM, Clynes R. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med. 2014 Sep;20(9):1043-9. doi: 10.1038/nm.3645. Epub 2014 Aug 17.
PubMed 25129481
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of the Role of the JAK-STAT Pathway in the Pathogenesis of Male Androgenetic Alopecia
- ClinicalTrials.gov ID
- NCT03694067
- Acronym / sponsor ID
- Atm567
- Conditions
- Androgenetic Alopecia
- Keywords
- Androgenetic, Alopecia, JAK, STAT
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Study start
- 15 Oct 2018 (actual)
- Primary completion
- 1 Dec 2019 (actual)
- Study completion
- 1 Dec 2019 (actual)
- First posted
- 3 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
It is a well known fact that the JAK-STAT pathway plays a pivotal role in the pathogenesis of alopecia areata. Both phosphorylated STAT 1 and 3 have been found to be upregulated in the disease. However, whether this pathway plays a role in other hair loss disorders remains unclear. The study aims at assessing STAT3 levels in male patients with androgenetic alopecia. The investigators hypothesize that STAT3 levels will be elevated (due to a previous study proving that JAK-STAT pathway is involved in non-immune mediated hair loss in mice.
Detailed description
Background and rationale Androgenetic alopecia occurs in men and women,and is characterised by the loss of hair from the scalp in a defined pattern. Determining factors appear to be genetic predisposition coupled with the presence of sufficient circulating androgen.
The transformation of testosterone into dihydrotestosterone(DHT) by type 2 5-alpha reductase, which causes hair miniaturization,is universally accepted as the main player in the disease's pathogenesis. Nonetheless,how DHT causes hair thinning is not well understood. New studies revealed that a lymphocytic microfolliculitis targeting the bulge epithelium along with deposits of epithelial basement membrane zone immunoreactants are frequent findings in androgenetic alopecia and could point toward an immunologically driven trigger.
Tyrosine kinases (TKs) are enzymes involved in intracellular signaling that catalyze the phosphorylation of tyrosine residues on protein substrates. They are key components of signaling pathways that drive any array of cellular responses including proliferation, differentiation, migration and survival. Janus kinases (JAKs) are specific TKs.
Signal transducer and activator of transcription (STAT) proteins are transcription factorsprimarily phosphorylated and activated by JAKs.The JAK-STAT pathway is utilized by cytokines including interleukins (ILs), interferons (IFNs), and other molecules to transmit signals from the cell membrane to the nucleus. Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis and vitiligo.
It is a well known fact that the JAK-STAT pathway plays a pivotal role in the pathogenesis of alopecia areata. Both phosphorylated STAT 1 and 3 have been found to be upregulated in the disease. However, whether this pathway plays a role in other hair loss disorders remains unclear. A study showedthat topical treatment of mouse and human skin with small molecule inhibitors of the JAK-STATpathway resulted in rapid onset of anagen and subsequent hair growth. It was shown that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ. These findings indicate that the JAK-STAT pathway may be involved, not only in immune-mediated hair loss (alopecia areata), but also in the normal hair cycle.
This current study aims at assessing STAT3 levels in patients with androgenetic alopecia, in an attempt to detect a possible role of the JAK-STAT pathway in the pathogenesis of the disease.
Objective:
The objective is to compare tissue levels of STAT3 in androgen-dependant areas in male androgenetic alopecia patients with their level in non-involved, non-androgen dependant areas (occipital scalp) in the same subjects.
Population of study \& disease condition (e.g women with hepatitis, ............) Males with androgenetic alopecia
Background and demographic characteristics( e.g age,.......)
- Age above 18 years.
- Males
Interventions :
Each subject will be subjected to:
- Informed consent.
- Detailed history and clinical evaluation to determine severity of disease.
- Punch biopsies (1mm) of affected area of scalp (androgen dependent area) from 25 patients with androgenetic alopecia.
- Punch biopsies(1mm) of normal area of scalp from occipital scalp (non-androgen dependent area) from the same 25 patients
- Quantification of STAT3 by polymerase chain reaction (PCR).
Sample size (number of participants included)
- 25 participants (That will serve as both patients and controls)
- Sample size calculation was done using G ⃰ Power 3.1.9.2.
Possible. Risk Bleeding, secondary infection, scarring.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Androgenetic alopecia patients | – | Other: Punch skin biopsyTwo 1 mm scalp punch skin biopsy will be taken per patient |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Specialized dermatology clinic at Cairo University
Key inclusion criteria (1 listed)
- Males with androgenetic alopecia not receiving topical treatment nor systemic treatment for hair loss for at least 6 month prior to the study
Key exclusion criteria (1 listed)
- Patients with localized or generalized hair loss due to causes other than androgenetic alopecia.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Punch skin biopsyOne 1 mm punch biopsy will be taken from the patients from balding scalp. Another 1 mm punch biopsy will be taken from an area of occipital non-balding scalp of the same individual. Local anesthesia will be injected around the biopsy site beforehand. | Other | Androgenetic alopecia patients |
Primary outcome
Different in STAT3
Time frame: 6 months
STAT3 levels in androgen-dependant areas compared to non-involved areas from occipital scalp(in an attempt to assess the possible role of the JAK-STAT pathway in androgenetic alopecia).
1 secondary outcome
Correlating STAT3 with severity
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2020.
- Background: PubMed 28139263Damsky W, King BA. JAK inhibitors in dermatology: The promise of a new drug class. J Am Acad Dermatol. 2017 Apr;76(4):736-744. doi: 10.1016/j.jaad.2016.12.005. Epub 2017 Jan 28.
- Background: PubMed 14585162Ellis JA, Sinclair R, Harrap SB. Androgenetic alopecia: pathogenesis and potential for therapy. Expert Rev Mol Med. 2002 Nov 19;4(22):1-11. doi: 10.1017/S1462399402005112.
- Background: PubMed 26601320Harel S, Higgins CA, Cerise JE, Dai Z, Chen JC, Clynes R, Christiano AM. Pharmacologic inhibition of JAK-STAT signaling promotes hair growth. Sci Adv. 2015 Oct 23;1(9):e1500973. doi: 10.1126/sciadv.1500973. eCollection 2015 Oct.
- Background: PubMed 22134564Magro CM, Rossi A, Poe J, Manhas-Bhutani S, Sadick N. The role of inflammation and immunity in the pathogenesis of androgenetic alopecia. J Drugs Dermatol. 2011 Dec;10(12):1404-11.
- Background: PubMed 25587654O'Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A. The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med. 2015;66:311-28. doi: 10.1146/annurev-med-051113-024537.
- Background: PubMed 20584561Paniagua RT, Fiorentino DF, Chung L, Robinson WH. Tyrosine kinases in inflammatory dermatologic disease. J Am Acad Dermatol. 2011 Aug;65(2):389-403. doi: 10.1016/j.jaad.2010.04.026. Epub 2010 Jun 26.
- Background: PubMed 26633291Schwartz DM, Bonelli M, Gadina M, O'Shea JJ. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat Rev Rheumatol. 2016 Jan;12(1):25-36. doi: 10.1038/nrrheum.2015.167. Epub 2015 Dec 3.
- Background: PubMed 15020666Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci. 2004 Mar 15;117(Pt 8):1281-3. doi: 10.1242/jcs.00963. No abstract available.
- Background: PubMed 11511857Whiting DA. Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss. J Am Acad Dermatol. 2001 Sep;45(3 Suppl):S81-6. doi: 10.1067/mjd.2001.117428.
- Background: PubMed 25129481Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, de Jong A, Harel S, DeStefano GM, Rothman L, Singh P, Petukhova L, Mackay-Wiggan J, Christiano AM, Clynes R. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med. 2014 Sep;20(9):1043-9. doi: 10.1038/nm.3645. Epub 2014 Aug 17.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Akmal S Hassan, MD study director
Cairo University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Androgenetic Alopecia, run by Cairo University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Different in STAT3 (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03694067, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2020.