PodoconiosisNCT01939431
Genetic and Other Aspects of Podoconiosis
An observational study of Podoconiosis, run by National Human Genome Research Institute (NHGRI) at 1 site in Ethiopia.
Trial summary
Background: Podoconiosis is a disease of the lymph vessels in the legs and feet. It is caused by long-term barefoot exposure to irritant soils, such as those in volcanic areas. It causes severe swelling and disfigurement, as well as infection and chronic pain. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Podoconiosis
- How many people
- 76 participants
- Where
- 1 siteEthiopia
- Study dates
- 20 Aug 2013to 30 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with podoconiosis@@@@@@
Who may be able to join
- All individuals included in our study will be adults (greater than or equal to 18 years) because the average age of onset of the disease is during the third decade of life. In addition, in Ethiopia the legal age to give independent consent for research is 18 years or older. Previous studies have shown that diagnosis of podoconiosis using physical diagnostic criteria in endemic highland areas is highly accurate. To rule out filarial elephantiasis, a rapid ICT card test will be done. Advanced stage podoconiosis cases will be included in the study based on prior assessment of an experienced surgeon (Dr Wendemagegn Enbiale Yeshanehe) who assures eligibility for nodulectomy if a patient with clinical stage III, IV or V podoconiosis has fibrotic nodules. Early clinical stage podoconiosis patients will be individuals with negative filarial test and at clinical stages I or II. Controls will be individuals with no past or current history, signs and symptoms of podoconiosis and no family history of podoconiosis.
Who cannot join
- -In addition to clinical criteria that make patients and controls non-eligible to undergo surgery, we will also exclude individuals with skin infection, skin lesion at the prospective biopsy site, medical contradictions to biopsy, history of adenolymphangitis during the previous 2 weeks, topical steroid treatment during the previous 2 weeks, with biologically related family members that are included in the study, recent infection, use of systemic antibiotics and use of systemic steroids. Attempts will be made to enroll an equal number of men and women. No prisoners, pregnant women or fetuses will be included in this study.
Trial locations and contacts
1 site in 1 country.
Ethiopia1 site
Bahir Dar University, Medical and Healath Science College
Bahir Dar
About this study
Official title: Investigation of the Pathogenesis of Podoconiosis Using RNA-seq and Immunopathologic Approaches
Background:
- Podoconiosis is a disease of the lymph vessels in the legs and feet. It is caused by long-term barefoot exposure to irritant soils, such as those in volcanic areas. It causes severe swelling and disfigurement, as well as infection and chronic pain. It mostly affects people who live in tropical Africa, Central and South America, and India. The reasons why some people develop this disease and others do not is not well understood. Researchers want to study people with the disease and healthy volunteers in Ethiopia. They will collect skin and blood samples to study genetic and other aspects of the disease.
Read more
Objectives:
- To collect skin and blood samples to study genetic and other aspects of podoconiosis.
Eligibility:
- Individuals at least 18 years of age who have podoconiosis (early stage or advanced stage).
- Healthy volunteers at least 18 years of age.
- Participants will be recruited from a study clinic and hospital in Ethiopia.
Design:
- Participants will be screened with a physical exam and medical history.
- Blood samples will be collected. A skin biopsy will be performed to collect tissue for study. People who have podoconiosis will provide affected and unaffected tissue. Healthy volunteers will provide a single skin biopsy sample.
- Treatment will not be provided as part of this study.
Read the detailed description
This research protocol is designed to study gene expression differentials and immunologic profile and histopatologic presentation of podoconiosis by comparing cases and controls in Ethiopia. Podoconiosis is a geochemical lymphedema of the lower limbs resulting from long term barefoot exposure to irritant red clay soils of volcanic origin. The disease imposes huge social and economic burden and affects more than 4 million individuals in tropical Africa, Central and South America, and North India. The pathologic changes in podoconiosis are still not known and the histopathologic features of the disease have not been well studied. Our recent genome-wide association study revealed that variants in HLA class II genes (HLA-DRB1, -DQB1, and -DQA1) are associated with podoconiosis, and suggests that the disease may be a Tcell mediated inflammatory condition (New Eng J Med 2012). The objectives of the present study are to investigate the immunologic profiles and gene expression differences between podoconiosis patients and healthy controls. The study will include 150 subjects consisting of 100 cases (50 early stage and 50 advanced stage), and 50 controls from Ethiopia. Anonymized discarded skin tissue samples will be obtained from excised nodules of 50 advanced stage patients that undergo nodulectomy (surgical excisions of nodules) in Bahir Dar Hospital. Punch biopsies will be obtained from affected skin tissues (epidermis and dermis) of 50 early stage podoconiosis patients that attend routine treatment in Dur-Bete
Podoconiosis Center, and normal skin tissues (epidermis and dermis) of 50 control subjects undergoing orthopedic surgery of the lower legs in Bahir Dar Hospital. We will also obtain 6 mm skin tissue punch biopsies from the unaffected areas in the lower limbs of all podoconiosis patients and peripheral blood samples (PBS) from all study subjects. RNA from PBS and T cells separated from other cells will be extracted in Armauer Hansen Research Institute of Ethiopia (AHRI) and will be shipped along with skin biopsies that will be kept in liquid nitrogen to CRGGH/NHGRI. Back-up samples will be kept in AHRI. We will use RNA-seq, a high throughput RNA sequencing technology, to characterize the transcriptome by sequencing complementary DNAs (cDNAs) followed by mapping of the sequence reads to the genome. Generation of double-stranded cDNA from mRNA and quantitation of cDNA concentration will
be done in our lab at NIH. Sequencing will be done by a commercial high throughput sequencing company, SeqWright (Houston, TX) an Illumina certified service provider. Immunologic profiling will be done using a FACSCalibur type flow cytometry. Analysis of data will be done using appropriate statistical programs and pipeline suites as described below. This study is expected to reveal differential gene expression between podoconiosis patients and controls. Furthermore, it will chart the evolution of gene expression signatures in podoconiosis patients through the different clinical stages of the disease. The findings could potentially lead to biomarkers that complement the clinical and genetic characteristics of the disease. The histopathological studies will provide a rich description of cutaneous and immunologic response across the spectrum of the disease. The integration of clinical, immunological, genetic, cellular and molecular characteristics of the disease will facilitate the development of a model for the natural history and pathogenesis of this neglected tropical disease.
- Conditions
- Podoconiosis
- Keywords
- Podoconiosis, Ethiopian
- Medical subject headings
- Elephantiasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Advanced | advanced stage podoconiosis | |
| Control | non-podoconiosis controls | |
| Early | early stage podoconiosis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Natural History
To study genetic and other aspects of podoconiosis using data from skin and blood samples.
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2013 (estimated)
- Study start20 Aug 2013
- Primary completion30 Dec 2019
- Study completion30 Dec 2019
Why it stopped: Slow/Insufficient accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for PodoconiosisStudies 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
- Other
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Charles N Rotimi, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01939431
- Sponsor's protocol ID
- 999913129
- Other IDs
- 13-HG-N129
- Status last verified
- Jan 2021
- First submitted
- 5 Sep 2013
- Last updated
- 14 Jan 2021
- Results posted
- No
Publications
Bullard JH, Purdom E, Hansen KD, Dudoit S. Evaluation of statistical methods for normalization and differential expression in mRNA-Seq experiments. BMC Bioinformatics. 2010 Feb 18;11:94. doi: 10.1186/1471-2105-11-94.
PubMed 20167110Cheng WC, Shu WY, Li CY, Tsai ML, Chang CW, Chen CR, Cheng HT, Wang TH, Hsu IC. Intra- and inter-individual variance of gene expression in clinical studies. PLoS One. 2012;7(6):e38650. doi: 10.1371/journal.pone.0038650. Epub 2012 Jun 18.
PubMed 22723873Davey G, Gebrehanna E, Adeyemo A, Rotimi C, Newport M, Desta K. Podoconiosis: a tropical model for gene-environment interactions? Trans R Soc Trop Med Hyg. 2007 Jan;101(1):91-6. doi: 10.1016/j.trstmh.2006.05.002. Epub 2006 Aug 1.
PubMed 16884751
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Pathogenesis of Podoconiosis Using RNA-seq and Immunopathologic Approaches
- ClinicalTrials.gov ID
- NCT01939431
- Acronym / sponsor ID
- 999913129
- Conditions
- Podoconiosis
- Keywords
- Podoconiosis, Ethiopian
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Slow/Insufficient accrual
- Enrolment
- 76 participants (actual)
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- 20 Aug 2013 (actual)
- Primary completion
- 30 Dec 2019 (actual)
- Study completion
- 30 Dec 2019 (actual)
- First posted
- 11 Sep 2013 (estimated)
- 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.
Background:
- Podoconiosis is a disease of the lymph vessels in the legs and feet. It is caused by long-term barefoot exposure to irritant soils, such as those in volcanic areas. It causes severe swelling and disfigurement, as well as infection and chronic pain. It mostly affects people who live in tropical Africa, Central and South America, and India. The reasons why some people develop this disease and others do not is not well understood. Researchers want to study people with the disease and healthy volunteers in Ethiopia. They will collect skin and blood samples to study genetic and other aspects of the disease.
Objectives:
- To collect skin and blood samples to study genetic and other aspects of podoconiosis.
Eligibility:
- Individuals at least 18 years of age who have podoconiosis (early stage or advanced stage).
- Healthy volunteers at least 18 years of age.
- Participants will be recruited from a study clinic and hospital in Ethiopia.
Design:
- Participants will be screened with a physical exam and medical history.
- Blood samples will be collected. A skin biopsy will be performed to collect tissue for study. People who have podoconiosis will provide affected and unaffected tissue. Healthy volunteers will provide a single skin biopsy sample.
- Treatment will not be provided as part of this study.
Detailed description
This research protocol is designed to study gene expression differentials and immunologic profile and histopatologic presentation of podoconiosis by comparing cases and controls in Ethiopia. Podoconiosis is a geochemical lymphedema of the lower limbs resulting from long term barefoot exposure to irritant red clay soils of volcanic origin. The disease imposes huge social and economic burden and affects more than 4 million individuals in tropical Africa, Central and South America, and North India. The pathologic changes in podoconiosis are still not known and the histopathologic features of the disease have not been well studied. Our recent genome-wide association study revealed that variants in HLA class II genes (HLA-DRB1, -DQB1, and -DQA1) are associated with podoconiosis, and suggests that the disease may be a Tcell mediated inflammatory condition (New Eng J Med 2012). The objectives of the present study are to investigate the immunologic profiles and gene expression differences between podoconiosis patients and healthy controls. The study will include 150 subjects consisting of 100 cases (50 early stage and 50 advanced stage), and 50 controls from Ethiopia. Anonymized discarded skin tissue samples will be obtained from excised nodules of 50 advanced stage patients that undergo nodulectomy (surgical excisions of nodules) in Bahir Dar Hospital. Punch biopsies will be obtained from affected skin tissues (epidermis and dermis) of 50 early stage podoconiosis patients that attend routine treatment in Dur-Bete
Podoconiosis Center, and normal skin tissues (epidermis and dermis) of 50 control subjects undergoing orthopedic surgery of the lower legs in Bahir Dar Hospital. We will also obtain 6 mm skin tissue punch biopsies from the unaffected areas in the lower limbs of all podoconiosis patients and peripheral blood samples (PBS) from all study subjects. RNA from PBS and T cells separated from other cells will be extracted in Armauer Hansen Research Institute of Ethiopia (AHRI) and will be shipped along with skin biopsies that will be kept in liquid nitrogen to CRGGH/NHGRI. Back-up samples will be kept in AHRI. We will use RNA-seq, a high throughput RNA sequencing technology, to characterize the transcriptome by sequencing complementary DNAs (cDNAs) followed by mapping of the sequence reads to the genome. Generation of double-stranded cDNA from mRNA and quantitation of cDNA concentration will
be done in our lab at NIH. Sequencing will be done by a commercial high throughput sequencing company, SeqWright (Houston, TX) an Illumina certified service provider. Immunologic profiling will be done using a FACSCalibur type flow cytometry. Analysis of data will be done using appropriate statistical programs and pipeline suites as described below. This study is expected to reveal differential gene expression between podoconiosis patients and controls. Furthermore, it will chart the evolution of gene expression signatures in podoconiosis patients through the different clinical stages of the disease. The findings could potentially lead to biomarkers that complement the clinical and genetic characteristics of the disease. The histopathological studies will provide a rich description of cutaneous and immunologic response across the spectrum of the disease. The integration of clinical, immunological, genetic, cellular and molecular characteristics of the disease will facilitate the development of a model for the natural history and pathogenesis of this neglected tropical disease.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Advanced | – | –advanced stage podoconiosis |
| Control | – | –non-podoconiosis controls |
| Early | – | –early stage podoconiosis |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with podoconiosis@@@@@@
Key inclusion criteria (1 listed)
- All individuals included in our study will be adults (greater than or equal to 18 years) because the average age of onset of the disease is during the third decade of life. In addition, in Ethiopia the legal age to give independent consent for research is 18 years or older. Previous studies have shown that diagnosis of podoconiosis using physical diagnostic criteria in endemic highland areas is highly accurate. To rule out filarial elephantiasis, a rapid ICT card test will be done. Advanced stage podoconiosis cases will be included in the study based on prior assessment of an experienced surgeon (Dr Wendemagegn Enbiale Yeshanehe) who assures eligibility for nodulectomy if a patient with clinical stage III, IV or V podoconiosis has fibrotic nodules. Early clinical stage podoconiosis patients will be individuals with negative filarial test and at clinical stages I or II. Controls will be individuals with no past or current history, signs and symptoms of podoconiosis and no family history of podoconiosis.
Key exclusion criteria (1 listed)
- -In addition to clinical criteria that make patients and controls non-eligible to undergo surgery, we will also exclude individuals with skin infection, skin lesion at the prospective biopsy site, medical contradictions to biopsy, history of adenolymphangitis during the previous 2 weeks, topical steroid treatment during the previous 2 weeks, with biologically related family members that are included in the study, recent infection, use of systemic antibiotics and use of systemic steroids. Attempts will be made to enroll an equal number of men and women. No prisoners, pregnant women or fetuses will be included in this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Natural History
Time frame: Ongoing
To study genetic and other aspects of podoconiosis using data from skin and blood samples.
Results and safety
The study was stopped early (reason given: Slow/Insufficient accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2021.
- Background: PubMed 20167110Bullard JH, Purdom E, Hansen KD, Dudoit S. Evaluation of statistical methods for normalization and differential expression in mRNA-Seq experiments. BMC Bioinformatics. 2010 Feb 18;11:94. doi: 10.1186/1471-2105-11-94.
- Background: PubMed 22723873Cheng WC, Shu WY, Li CY, Tsai ML, Chang CW, Chen CR, Cheng HT, Wang TH, Hsu IC. Intra- and inter-individual variance of gene expression in clinical studies. PLoS One. 2012;7(6):e38650. doi: 10.1371/journal.pone.0038650. Epub 2012 Jun 18.
- Background: PubMed 16884751Davey G, Gebrehanna E, Adeyemo A, Rotimi C, Newport M, Desta K. Podoconiosis: a tropical model for gene-environment interactions? Trans R Soc Trop Med Hyg. 2007 Jan;101(1):91-6. doi: 10.1016/j.trstmh.2006.05.002. Epub 2006 Aug 1.
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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.
Charles N Rotimi, M.D. principal investigator
National Human Genome Research Institute (NHGRI)
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 Podoconiosis, run by National Human Genome Research Institute (NHGRI) at 1 site in Ethiopia.
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: stopped early, as of the sponsor's last update on 14 Jan 2021. 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 Ethiopia. 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 was stopped early (reason given: Slow/Insufficient accrual). Results are not available in the source record.
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?
Natural History (time frame: Ongoing). 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 NCT01939431, which also lists 3 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 14 Jan 2021.