Epidermolysis BullosaNCT03269474
Computational Drug Repurposing for All EBS Cases
An observational study of Epidermolysis Bullosa and Healthy, run by Joyce Teng at 1 site in United States.
Trial summary
The study will compare gene expression differences between blistered and non-blistered skin from individuals with all subtypes of EB, as well as normal skin from non-EB subjects. State of the art computational analysis will be performed to help identify new drugs that might help all EB wound healing and reduce pain. Read more about this study
- Who is it for?
- Ages 0 years and olderHealthy volunteers can take part
- Conditions the study is for
- Epidermolysis Bullosa, Healthy, Genetic Skin Disease
- What is being tested?
- Experimental Group
- Type of treatment
- Surgery or procedure
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Nov 2017to 31 Dec 2024
- 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 0 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Subject of all ages with either 1) a diagnosis of EB subjects or 2) healthy, non-EB subjects
Who may be able to join
- Subjects of all ages
- Diagnosis of all subtypes of EB subjects
- Healthy, non-EB subjects
- Ability to complete study visit to collect tissue and blood specimen
Who cannot join
- Pregnancy, breast feeding
- Prior history of liver disease
- Serious known concurrent medical illness or infection, which could potentially present a safety risk and/or prevent tissue collection from subjects
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Pediatric Dermatology Clinic at Stanford Children's Hospital
Palo Alto, California, 94304
Monica Martin, 650-723-0636, PediatricDermStudy@stanford.edu
Elidia V Tafoya, MPH, 650-724-1982, PediatricDermStudy@stanford.edu
About this study
Official title: Computational Drug Repurposing for All Epidermolysis Bullosa Simplex (EBS) Cases
The study will compare gene expression differences between blistered and non-blistered skin from individuals with all subtypes of EB, as well as normal skin from non-EB subjects. State of the art computational analysis will be performed to help identify new drugs that might help all EB wound healing and reduce pain. Researchers will focus on drugs that have already been approved for treatment of other dermatologic or non-dermatologic diseases, and therefore be repurposed for treatment of EB. Drug development is a very expensive process taking decades for execution. Drug repurposing on the other hand, significantly reduces the cost and shortens the amount of time that is needed to bring effective treatments to clinical use. To date, there is no specific treatment targeting the physiology and immunologic response in EB patients during wound healing. Market availability of repurposed medications will provide all EB patients rapid access to treatments, thus improving their quality of life.
Read the detailed description
Although gene, cell, and protein-based therapies are in development for patients suffering from all subtypes of epidermolysis bullosa (EB), new pharmacological treatments are in dire need. Characterizing molecular changes in EB, including gene expression, can identify new therapeutic targets and drugs that modulate those targets. However, sifting through gene expression information to identify the most promising drug targets is a complex data challenge. The goal of the study will identify a computational approach to evaluate and identify existing drugs approved for other diseases that can be repurposed for EB patients. The study will perform an unprecedented characterization of gene expression changes in EB patients compared to healthy, non-EB individuals across multiple tissues. Using a validated computational drug discovery platform, researchers will analyze gene expression and drug data using unique algorithms. In the first year, a list of ten, safety drugs more probable to treat the EB disease state will be identified. The most promising drugs discovered will then be tested in the clinic setting.
- Conditions
- Epidermolysis Bullosa, Healthy, Genetic Skin Disease, Epidermolysis Bullosa Simplex, Epidermolysis Bullosa, Junctional, Epidermolysis Bullosa Dystrophica
- Being tested
- Experimental Group
- Keywords
- epidermolysis bullosa, genetic expression, drug repurposing, computational approaches, drug discovery
- Medical subject headings
- Epidermolysis Bullosa, Skin Diseases, Genetic, Epidermolysis Bullosa Simplex, Epidermolysis Bullosa, Junctional, Epidermolysis Bullosa Dystrophica
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experimental GroupProcedure or surgery
Subjects with EB diagnosis
| Study group | Role | What they receive |
|---|---|---|
| Experimental Group | Blood and tissue specimen will be collected from subjects with an EB diagnosis. Tissue specimen will be collected from blistered and nonblistered skin. Receives: Procedure: Experimental Group | |
| Control Group | Blood and tissue specimen will be collected from healthy subjects with non-EB. Tissue specimen will be collected from an inconspicuous skin area. Receives: Procedure: Experimental Group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterize gene expression changes in EB using RNA sequencing (RNA-seq) and Computational Profiling Potential Drug Targets
Using bioinformatic algorithms to identify changes in gene expression and review of over 2000 FDA-approved drugs based on predicted modulation of gene expression changes using a computational evolutionary algorithm system.
Measured: Through the completion of study in 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2017
- Study start28 Nov 2017
- Primary completion30 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Epidermolysis BullosaStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Joyce Teng
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Joyce Teng, Stanford University
- Investigators
- Joyce M Teng, MD, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03269474
- Sponsor's protocol ID
- 41142
- Status last verified
- Feb 2024
- First submitted
- 21 Aug 2017
- Last updated
- 13 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: As of now, there are no plans to share the data with other researchers. Once the outcome measures have been accomplished, the research team will publish results for the entire clinicaltrials.gov community and researchers for this vulnerable population study.
Publications
McLaren PJ, Mayne M, Rosser S, Moffatt T, Becker KG, Plummer FA, Fowke KR. Antigen-specific gene expression profiles of peripheral blood mononuclear cells do not reflect those of T-lymphocyte subsets. Clin Diagn Lab Immunol. 2004 Sep;11(5):977-82. doi: 10.1128/CDLI.11.5.977-982.2004.
PubMed 15358662Sleasman JW, Leon BH, Aleixo LF, Rojas M, Goodenow MM. Immunomagnetic selection of purified monocyte and lymphocyte populations from peripheral blood mononuclear cells following cryopreservation. Clin Diagn Lab Immunol. 1997 Nov;4(6):653-8. doi: 10.1128/cdli.4.6.653-658.1997.
PubMed 9384284Bray NL, Pimentel H, Melsted P, Pachter L. Near-optimal probabilistic RNA-seq quantification. Nat Biotechnol. 2016 May;34(5):525-7. doi: 10.1038/nbt.3519. Epub 2016 Apr 4.
PubMed 27043002Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010 Jan 1;26(1):139-40. doi: 10.1093/bioinformatics/btp616. Epub 2009 Nov 11.
PubMed 19910308Law V, Knox C, Djoumbou Y, Jewison T, Guo AC, Liu Y, Maciejewski A, Arndt D, Wilson M, Neveu V, Tang A, Gabriel G, Ly C, Adamjee S, Dame ZT, Han B, Zhou Y, Wishart DS. DrugBank 4.0: shedding new light on drug metabolism. Nucleic Acids Res. 2014 Jan;42(Database issue):D1091-7. doi: 10.1093/nar/gkt1068. Epub 2013 Nov 6.
PubMed 24203711Sugaya N, Kanai S, Furuya T. Dr. PIAS 2.0: an update of a database of predicted druggable protein-protein interactions. Database (Oxford). 2012 Oct 10;2012:bas034. doi: 10.1093/database/bas034. Print 2012.
PubMed 23060433Subramanian A, Kuehn H, Gould J, Tamayo P, Mesirov JP. GSEA-P: a desktop application for Gene Set Enrichment Analysis. Bioinformatics. 2007 Dec 1;23(23):3251-3. doi: 10.1093/bioinformatics/btm369. Epub 2007 Jul 20.
PubMed 17644558Cohn HI, Teng JM. Advancement in management of epidermolysis bullosa. Curr Opin Pediatr. 2016 Aug;28(4):507-16. doi: 10.1097/MOP.0000000000000380.
PubMed 27386970Uitto J, Bruckner-Tuderman L, Christiano AM, McGrath JA, Has C, South AP, Kopelan B, Robinson EC. Progress toward Treatment and Cure of Epidermolysis Bullosa: Summary of the DEBRA International Research Symposium EB2015. J Invest Dermatol. 2016 Feb;136(2):352-358. doi: 10.1016/j.jid.2015.10.050.
PubMed 26802230Nystrom A, Thriene K, Mittapalli V, Kern JS, Kiritsi D, Dengjel J, Bruckner-Tuderman L. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms. EMBO Mol Med. 2015 Sep;7(9):1211-28. doi: 10.15252/emmm.201505061.
PubMed 26194911Wally V, Kitzmueller S, Lagler F, Moder A, Hitzl W, Wolkersdorfer M, Hofbauer P, Felder TK, Dornauer M, Diem A, Eiler N, Bauer JW. Topical diacerein for epidermolysis bullosa: a randomized controlled pilot study. Orphanet J Rare Dis. 2013 May 7;8:69. doi: 10.1186/1750-1172-8-69.
PubMed 23651789Li J, Zheng S, Chen B, Butte AJ, Swamidass SJ, Lu Z. A survey of current trends in computational drug repositioning. Brief Bioinform. 2016 Jan;17(1):2-12. doi: 10.1093/bib/bbv020. Epub 2015 Mar 31.
PubMed 25832646Low YS, Daugherty AC, Schroeder EA, Chen W, Seto T, Weber S, Lim M, Hastie T, Mathur M, Desai M, Farrington C, Radin AA, Sirota M, Kenkare P, Thompson CA, Yu PP, Gomez SL, Sledge GW Jr, Kurian AW, Shah NH. Synergistic drug combinations from electronic health records and gene expression. J Am Med Inform Assoc. 2017 May 1;24(3):565-576. doi: 10.1093/jamia/ocw161.
PubMed 27940607Bchetnia M, Tremblay ML, Leclerc G, Duperee A, Powell J, McCuaig C, Morin C, Legendre-Guillemin V, Laprise C. Expression signature of epidermolysis bullosa simplex. Hum Genet. 2012 Mar;131(3):393-406. doi: 10.1007/s00439-011-1077-7. Epub 2011 Aug 30.
PubMed 21877134Roth W, Reuter U, Wohlenberg C, Bruckner-Tuderman L, Magin TM. Cytokines as genetic modifiers in K5-/- mice and in human epidermolysis bullosa simplex. Hum Mutat. 2009 May;30(5):832-41. doi: 10.1002/humu.20981.
PubMed 19267394
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Computational Drug Repurposing for All Epidermolysis Bullosa Simplex (EBS) Cases
- ClinicalTrials.gov ID
- NCT03269474
- Acronym / sponsor ID
- 41142
- Conditions
- Epidermolysis Bullosa, Healthy, Genetic Skin Disease, Epidermolysis Bullosa Simplex, Epidermolysis Bullosa, Junctional, Epidermolysis Bullosa Dystrophica
- Keywords
- epidermolysis bullosa, genetic expression, drug repurposing, computational approaches, drug discovery
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Joyce TengUniversity, hospital or other
- Study start
- 28 Nov 2017 (actual)
- Primary completion
- 30 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 31 Aug 2017 (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.
The study will compare gene expression differences between blistered and non-blistered skin from individuals with all subtypes of EB, as well as normal skin from non-EB subjects. State of the art computational analysis will be performed to help identify new drugs that might help all EB wound healing and reduce pain. Researchers will focus on drugs that have already been approved for treatment of other dermatologic or non-dermatologic diseases, and therefore be repurposed for treatment of EB. Drug development is a very expensive process taking decades for execution. Drug repurposing on the other hand, significantly reduces the cost and shortens the amount of time that is needed to bring effective treatments to clinical use. To date, there is no specific treatment targeting the physiology and immunologic response in EB patients during wound healing. Market availability of repurposed medications will provide all EB patients rapid access to treatments, thus improving their quality of life.
Detailed description
Although gene, cell, and protein-based therapies are in development for patients suffering from all subtypes of epidermolysis bullosa (EB), new pharmacological treatments are in dire need. Characterizing molecular changes in EB, including gene expression, can identify new therapeutic targets and drugs that modulate those targets. However, sifting through gene expression information to identify the most promising drug targets is a complex data challenge. The goal of the study will identify a computational approach to evaluate and identify existing drugs approved for other diseases that can be repurposed for EB patients. The study will perform an unprecedented characterization of gene expression changes in EB patients compared to healthy, non-EB individuals across multiple tissues. Using a validated computational drug discovery platform, researchers will analyze gene expression and drug data using unique algorithms. In the first year, a list of ten, safety drugs more probable to treat the EB disease state will be identified. The most promising drugs discovered will then be tested in the clinic setting.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental Group | – | Procedure: Experimental GroupBlood and tissue specimen will be collected from subjects with an EB diagnosis. Tissue specimen will be collected from blistered and nonblistered skin. |
| Control Group | – | Procedure: Experimental GroupBlood and tissue specimen will be collected from healthy subjects with non-EB. Tissue specimen will be collected from an inconspicuous skin area. |
Who may qualify
- Ages
- 0 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Subject of all ages with either 1) a diagnosis of EB subjects or 2) healthy, non-EB subjects
Key inclusion criteria (4 listed)
- Subjects of all ages
- Diagnosis of all subtypes of EB subjects
- Healthy, non-EB subjects
- Ability to complete study visit to collect tissue and blood specimen
Key exclusion criteria (3 listed)
- Pregnancy, breast feeding
- Prior history of liver disease
- Serious known concurrent medical illness or infection, which could potentially present a safety risk and/or prevent tissue collection from subjects
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 |
|---|---|---|
| Experimental GroupSubjects with EB diagnosis | Procedure or surgery | Control Group, Experimental Group |
Primary outcome
Characterize gene expression changes in EB using RNA sequencing (RNA-seq) and Computational Profiling Potential Drug Targets
Time frame: Through the completion of study in 1 year.
Using bioinformatic algorithms to identify changes in gene expression and review of over 2000 FDA-approved drugs based on predicted modulation of gene expression changes using a computational evolutionary algorithm system.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2024.
- Background: PubMed 15358662McLaren PJ, Mayne M, Rosser S, Moffatt T, Becker KG, Plummer FA, Fowke KR. Antigen-specific gene expression profiles of peripheral blood mononuclear cells do not reflect those of T-lymphocyte subsets. Clin Diagn Lab Immunol. 2004 Sep;11(5):977-82. doi: 10.1128/CDLI.11.5.977-982.2004.
- Background: PubMed 9384284Sleasman JW, Leon BH, Aleixo LF, Rojas M, Goodenow MM. Immunomagnetic selection of purified monocyte and lymphocyte populations from peripheral blood mononuclear cells following cryopreservation. Clin Diagn Lab Immunol. 1997 Nov;4(6):653-8. doi: 10.1128/cdli.4.6.653-658.1997.
- Background: PubMed 27043002Bray NL, Pimentel H, Melsted P, Pachter L. Near-optimal probabilistic RNA-seq quantification. Nat Biotechnol. 2016 May;34(5):525-7. doi: 10.1038/nbt.3519. Epub 2016 Apr 4.
- Background: PubMed 19910308Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010 Jan 1;26(1):139-40. doi: 10.1093/bioinformatics/btp616. Epub 2009 Nov 11.
- Background: PubMed 24203711Law V, Knox C, Djoumbou Y, Jewison T, Guo AC, Liu Y, Maciejewski A, Arndt D, Wilson M, Neveu V, Tang A, Gabriel G, Ly C, Adamjee S, Dame ZT, Han B, Zhou Y, Wishart DS. DrugBank 4.0: shedding new light on drug metabolism. Nucleic Acids Res. 2014 Jan;42(Database issue):D1091-7. doi: 10.1093/nar/gkt1068. Epub 2013 Nov 6.
- Background: PubMed 23060433Sugaya N, Kanai S, Furuya T. Dr. PIAS 2.0: an update of a database of predicted druggable protein-protein interactions. Database (Oxford). 2012 Oct 10;2012:bas034. doi: 10.1093/database/bas034. Print 2012.
- Background: PubMed 17644558Subramanian A, Kuehn H, Gould J, Tamayo P, Mesirov JP. GSEA-P: a desktop application for Gene Set Enrichment Analysis. Bioinformatics. 2007 Dec 1;23(23):3251-3. doi: 10.1093/bioinformatics/btm369. Epub 2007 Jul 20.
- Results publication: PubMed 27386970Cohn HI, Teng JM. Advancement in management of epidermolysis bullosa. Curr Opin Pediatr. 2016 Aug;28(4):507-16. doi: 10.1097/MOP.0000000000000380.
- Results publication: PubMed 26802230Uitto J, Bruckner-Tuderman L, Christiano AM, McGrath JA, Has C, South AP, Kopelan B, Robinson EC. Progress toward Treatment and Cure of Epidermolysis Bullosa: Summary of the DEBRA International Research Symposium EB2015. J Invest Dermatol. 2016 Feb;136(2):352-358. doi: 10.1016/j.jid.2015.10.050.
- Results publication: PubMed 26194911Nystrom A, Thriene K, Mittapalli V, Kern JS, Kiritsi D, Dengjel J, Bruckner-Tuderman L. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms. EMBO Mol Med. 2015 Sep;7(9):1211-28. doi: 10.15252/emmm.201505061.
- Results publication: PubMed 23651789Wally V, Kitzmueller S, Lagler F, Moder A, Hitzl W, Wolkersdorfer M, Hofbauer P, Felder TK, Dornauer M, Diem A, Eiler N, Bauer JW. Topical diacerein for epidermolysis bullosa: a randomized controlled pilot study. Orphanet J Rare Dis. 2013 May 7;8:69. doi: 10.1186/1750-1172-8-69.
- Results publication: PubMed 25832646Li J, Zheng S, Chen B, Butte AJ, Swamidass SJ, Lu Z. A survey of current trends in computational drug repositioning. Brief Bioinform. 2016 Jan;17(1):2-12. doi: 10.1093/bib/bbv020. Epub 2015 Mar 31.
- Individual participant dataSharing planned: No. As of now, there are no plans to share the data with other researchers. Once the outcome measures have been accomplished, the research team will publish results for the entire clinicaltrials.gov community and researchers for this vulnerable population study.
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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.
Joyce M Teng, MD, PhD principal investigator
Stanford 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 Epidermolysis Bullosa and Healthy, run by Joyce Teng at 1 site in United States.
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 4 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 13 Feb 2024. 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 United States. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Monica Martin (650-723-0636, momartin@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterize gene expression changes in EB using RNA sequencing (RNA-seq) and Computational Profiling Potential Drug Targets (time frame: Through the completion of study in 1 year.). 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 NCT03269474, which also lists 17 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 13 Feb 2024; AzTrials last refreshed its copy on 28 Oct 2026.