Influenza A Virus/H5N1 SubtypeNCT01074736
Host Genetic Susceptibility to Avian Influenza A/H5N1
An observational study of Influenza A Virus/H5N1 Subtype, run by South East Asia Infectious Disease Clinical Research Network at 1 site in Vietnam.
Trial summary
The identification and characterization of susceptibility loci for H5N1 infection in humans could have profound implications. The detection of host genetic factors may shed light on key pathogenic interactions between H5N1 and human cells, assisting in identifying the viral characteristics determining pandemic… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Influenza A Virus/H5N1 Subtype
- How many people
- 500 participants
- Where
- 1 siteVietnam
- Study dates
- Jul 2008to Oct 2010
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: * symptomatic cases with laboratory confirmed H5N1 infection will be eligible for inclusion. * Priority for recruitment will be given to cases from multi-case families in order tomaximize the probability of including cases with a genetic etiology.
Who may be able to join
- The individual had a clinically compatible illness (defined as respiratory symptoms and an abnormal chest x-ray or encephalitis), AND
- Influenza A/H5 RNA identified in a clinical sample by reverse transcription-polymerase chain reaction [RT-PCR], OR
- Influenza A/H5 cultured from a clinical sample, OR
- High titres (1:80 or higher) of anti-H5 antibodies by microneutralization in convalescent samples of patients who had a compatible illness but no or negative RT-PCR, AND
- The patient survived or if they died an archived biological specimen is available for potential DNA extraction, AND
- Valid, written consent is obtained.
- The biological parents and biological siblings of all the cases and any other family members linking two cases, AND
- Valid, written consent is obtained.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Host Genetic Susceptibility to Avian Influenza A/H5N1 in Vietnam, Thailand, Indonesia and Singapore
The identification and characterization of susceptibility loci for H5N1 infection in humans could have profound implications. The detection of host genetic factors may shed light on key pathogenic interactions between H5N1 and human cells, assisting in identifying the viral characteristics determining pandemic potential. In addition, the identification and verification of susceptibility loci would be followed by functional studies which might point the way to new therapeutic and preventive options.
The objective of this study is to investigate if host genetic factors are associated with susceptibility to influenza H5N1 illness
Read the detailed description
This is primarily an hypothesis screening exercise and while guesses based on biological plausibility are possible, a comprehensive analysis of genetic susceptibility can only be achieved by a whole genome approach. Therefore we will test for genetic linkage and association using a large number of Single Nucleotide Polymorphisms (SNPs) spanning the whole genome.
Principal Investigators have access to information on all surviving and deceased laboratory confirmed H5N1 cases. These cases will form the study base. The epidemiologist will attempt to make telephone contact with either the recovered patient or,if the patient died, the closest relative of the deceased patient. The proposed study will be explained and permission will be sought for the epidemiologist and a study nurse to visit the household to explain the study in greater detail, to offer an opportunity for questions and, if the subject agrees, to obtain informed consent for participation. If the epidemiologist has difficulty in making contact with the case or their family the local public authorities will be asked to assist in making contact. Eligible family members of H5N1 cases will be identified by face-to-face interviews with the surviving confirmed cases or close family members of deceased cases.
- Conditions
- Influenza A Virus/H5N1 Subtype
- Keywords
- influenza A/H5N1, host genetic susceptibility, genotyping
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2010 (estimated)
- Study startJul 2008
- Primary completionAug 2010
- Study completionOct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (56)Papers the sponsor has linked to this study.
- Other trials for Influenza A Virus/H5N1 SubtypeStudies 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
- Family based
- Time perspective
- Cross-sectional
- Enrolment
- 500 participants (actual)
Sponsor and investigators
- Lead sponsor
- South East Asia Infectious Disease Clinical Research Network
- Sponsor type
- Research network
- Collaborators
- University of Oxford, Wellcome Trust
- Investigators
- Tawee Chotpitayasunond, Professor, Principal investigator, Queen Sirikit National Institute of Child Health, Bangkok, ThailandHerawati Sudoyo, Dr., Principal investigator, Eijkman Institute for Molecular BiologyTran Hien Nguyen, Professor, Principal investigator, National Institute of Hygiene and Epidemiology, Hanoi, VietnamMartin Hibberd, Dr., Principal investigator, Genome Institute of Singapore, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01074736
- Sponsor's protocol ID
- SEA 007
- Status last verified
- Nov 2010
- First submitted
- 23 Feb 2010
- Last updated
- 4 Nov 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Albright FS, Orlando P, Pavia AT, Jackson GG, Cannon Albright LA. Evidence for a heritable predisposition to death due to influenza. J Infect Dis. 2008 Jan 1;197(1):18-24. doi: 10.1086/524064.
PubMed 18171280Apisarnthanarak A, Erb S, Stephenson I, Katz JM, Chittaganpitch M, Sangkitporn S, Kitphati R, Thawatsupha P, Waicharoen S, Pinitchai U, Apisarnthanarak P, Fraser VJ, Mundy LM. Seroprevalence of anti-H5 antibody among Thai health care workers after exposure to avian influenza (H5N1) in a tertiary care center. Clin Infect Dis. 2005 Jan 15;40(2):e16-8. doi: 10.1086/427034. Epub 2004 Dec 17.
PubMed 15655735Bauer M, Orescovic I, Schoell WM, Bianchi DW, Pertl B. Detection of maternal deoxyribonucleic acid in umbilical cord plasma by using fluorescent polymerase chain reaction amplification of short tandem repeat sequences. Am J Obstet Gynecol. 2002 Jan;186(1):117-20. doi: 10.1067/mob.2002.118306.
PubMed 11810096Beigel JH, Farrar J, Han AM, Hayden FG, Hyer R, de Jong MD, Lochindarat S, Nguyen TK, Nguyen TH, Tran TH, Nicoll A, Touch S, Yuen KY; Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5. Avian influenza A (H5N1) infection in humans. N Engl J Med. 2005 Sep 29;353(13):1374-85. doi: 10.1056/NEJMra052211. No abstract available.
PubMed 16192482Burgner D, Jamieson SE, Blackwell JM. Genetic susceptibility to infectious diseases: big is beautiful, but will bigger be even better? Lancet Infect Dis. 2006 Oct;6(10):653-63. doi: 10.1016/S1473-3099(06)70601-6.
PubMed 17008174Burton PR, Tobin MD, Hopper JL. Key concepts in genetic epidemiology. Lancet. 2005 Sep 10-16;366(9489):941-51. doi: 10.1016/S0140-6736(05)67322-9.
PubMed 16154023Buxton Bridges C, Katz JM, Seto WH, Chan PK, Tsang D, Ho W, Mak KH, Lim W, Tam JS, Clarke M, Williams SG, Mounts AW, Bresee JS, Conn LA, Rowe T, Hu-Primmer J, Abernathy RA, Lu X, Cox NJ, Fukuda K. Risk of influenza A (H5N1) infection among health care workers exposed to patients with influenza A (H5N1), Hong Kong. J Infect Dis. 2000 Jan;181(1):344-8. doi: 10.1086/315213.
PubMed 10608786Chan VS, Chan KY, Chen Y, Poon LL, Cheung AN, Zheng B, Chan KH, Mak W, Ngan HY, Xu X, Screaton G, Tam PK, Austyn JM, Chan LC, Yip SP, Peiris M, Khoo US, Lin CL. Homozygous L-SIGN (CLEC4M) plays a protective role in SARS coronavirus infection. Nat Genet. 2006 Jan;38(1):38-46. doi: 10.1038/ng1698. Epub 2005 Dec 20.
PubMed 16369534Colhoun HM, McKeigue PM, Davey Smith G. Problems of reporting genetic associations with complex outcomes. Lancet. 2003 Mar 8;361(9360):865-72. doi: 10.1016/s0140-6736(03)12715-8.
PubMed 12642066Densen P, Weiler JM, Griffiss JM, Hoffmann LG. Familial properdin deficiency and fatal meningococcemia. Correction of the bactericidal defect by vaccination. N Engl J Med. 1987 Apr 9;316(15):922-6. doi: 10.1056/NEJM198704093161506. No abstract available.
PubMed 3102964Gagneux P, Cheriyan M, Hurtado-Ziola N, van der Linden EC, Anderson D, McClure H, Varki A, Varki NM. Human-specific regulation of alpha 2-6-linked sialic acids. J Biol Chem. 2003 Nov 28;278(48):48245-50. doi: 10.1074/jbc.M309813200. Epub 2003 Sep 18.
PubMed 14500706Gilsdorf A, Boxall N, Gasimov V, Agayev I, Mammadzade F, Ursu P, Gasimov E, Brown C, Mardel S, Jankovic D, Pimentel G, Ayoub IA, Elassal EM, Salvi C, Legros D, Pessoa da Silva C, Hay A, Andraghetti R, Rodier G, Ganter B. Two clusters of human infection with influenza A/H5N1 virus in the Republic of Azerbaijan, February-March 2006. Euro Surveill. 2006;11(5):122-6.
PubMed 16757853Glaser L, Conenello G, Paulson J, Palese P. Effective replication of human influenza viruses in mice lacking a major alpha2,6 sialyltransferase. Virus Res. 2007 Jun;126(1-2):9-18. doi: 10.1016/j.virusres.2007.01.011. Epub 2007 Feb 20.
PubMed 17313986Hamano E, Hijikata M, Itoyama S, Quy T, Phi NC, Long HT, Ha LD, Ban VV, Matsushita I, Yanai H, Kirikae F, Kirikae T, Kuratsuji T, Sasazuki T, Keicho N. Polymorphisms of interferon-inducible genes OAS-1 and MxA associated with SARS in the Vietnamese population. Biochem Biophys Res Commun. 2005 Apr 22;329(4):1234-9. doi: 10.1016/j.bbrc.2005.02.101.
PubMed 15766558Haralambous E, Dolly SO, Hibberd ML, Litt DJ, Udalova IA, O'dwyer C, Langford PR, Simon Kroll J, Levin M. Factor H, a regulator of complement activity, is a major determinant of meningococcal disease susceptibility in UK Caucasian patients. Scand J Infect Dis. 2006;38(9):764-71. doi: 10.1080/00365540600643203.
PubMed 16938729
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Host Genetic Susceptibility to Avian Influenza A/H5N1 in Vietnam, Thailand, Indonesia and Singapore
- ClinicalTrials.gov ID
- NCT01074736
- Acronym / sponsor ID
- SEA 007
- Conditions
- Influenza A Virus/H5N1 Subtype
- Keywords
- influenza A/H5N1, host genetic susceptibility, genotyping
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 500 participants (actual)
- Lead sponsor
- South East Asia Infectious Disease Clinical Research NetworkResearch network
- Collaborators
- University of Oxford, Wellcome Trust
- Study start
- Jul 2008
- Primary completion
- Aug 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 24 Feb 2010 (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.
The identification and characterization of susceptibility loci for H5N1 infection in humans could have profound implications. The detection of host genetic factors may shed light on key pathogenic interactions between H5N1 and human cells, assisting in identifying the viral characteristics determining pandemic potential. In addition, the identification and verification of susceptibility loci would be followed by functional studies which might point the way to new therapeutic and preventive options.
The objective of this study is to investigate if host genetic factors are associated with susceptibility to influenza H5N1 illness
Detailed description
This is primarily an hypothesis screening exercise and while guesses based on biological plausibility are possible, a comprehensive analysis of genetic susceptibility can only be achieved by a whole genome approach. Therefore we will test for genetic linkage and association using a large number of Single Nucleotide Polymorphisms (SNPs) spanning the whole genome.
Principal Investigators have access to information on all surviving and deceased laboratory confirmed H5N1 cases. These cases will form the study base. The epidemiologist will attempt to make telephone contact with either the recovered patient or,if the patient died, the closest relative of the deceased patient. The proposed study will be explained and permission will be sought for the epidemiologist and a study nurse to visit the household to explain the study in greater detail, to offer an opportunity for questions and, if the subject agrees, to obtain informed consent for participation. If the epidemiologist has difficulty in making contact with the case or their family the local public authorities will be asked to assist in making contact. Eligible family members of H5N1 cases will be identified by face-to-face interviews with the surviving confirmed cases or close family members of deceased cases.
Study design
- Observational model
- Family based
- Time perspective
- Cross-sectional
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- * symptomatic cases with laboratory confirmed H5N1 infection will be eligible for inclusion. * Priority for recruitment will be given to cases from multi-case families in order tomaximize the probability of including cases with a genetic etiology.
Key inclusion criteria (8 listed)
- The individual had a clinically compatible illness (defined as respiratory symptoms and an abnormal chest x-ray or encephalitis), AND
- Influenza A/H5 RNA identified in a clinical sample by reverse transcription-polymerase chain reaction [RT-PCR], OR
- Influenza A/H5 cultured from a clinical sample, OR
- High titres (1:80 or higher) of anti-H5 antibodies by microneutralization in convalescent samples of patients who had a compatible illness but no or negative RT-PCR, AND
- The patient survived or if they died an archived biological specimen is available for potential DNA extraction, AND
Key exclusion criteria (0 listed)
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
Not reported in the source record.
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 4 Nov 2010.
- Background: PubMed 18171280Albright FS, Orlando P, Pavia AT, Jackson GG, Cannon Albright LA. Evidence for a heritable predisposition to death due to influenza. J Infect Dis. 2008 Jan 1;197(1):18-24. doi: 10.1086/524064.
- Background: PubMed 15655735Apisarnthanarak A, Erb S, Stephenson I, Katz JM, Chittaganpitch M, Sangkitporn S, Kitphati R, Thawatsupha P, Waicharoen S, Pinitchai U, Apisarnthanarak P, Fraser VJ, Mundy LM. Seroprevalence of anti-H5 antibody among Thai health care workers after exposure to avian influenza (H5N1) in a tertiary care center. Clin Infect Dis. 2005 Jan 15;40(2):e16-8. doi: 10.1086/427034. Epub 2004 Dec 17.
- Background: PubMed 11810096Bauer M, Orescovic I, Schoell WM, Bianchi DW, Pertl B. Detection of maternal deoxyribonucleic acid in umbilical cord plasma by using fluorescent polymerase chain reaction amplification of short tandem repeat sequences. Am J Obstet Gynecol. 2002 Jan;186(1):117-20. doi: 10.1067/mob.2002.118306.
- Background: PubMed 16192482Beigel JH, Farrar J, Han AM, Hayden FG, Hyer R, de Jong MD, Lochindarat S, Nguyen TK, Nguyen TH, Tran TH, Nicoll A, Touch S, Yuen KY; Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5. Avian influenza A (H5N1) infection in humans. N Engl J Med. 2005 Sep 29;353(13):1374-85. doi: 10.1056/NEJMra052211. No abstract available.
- Background: PubMed 17008174Burgner D, Jamieson SE, Blackwell JM. Genetic susceptibility to infectious diseases: big is beautiful, but will bigger be even better? Lancet Infect Dis. 2006 Oct;6(10):653-63. doi: 10.1016/S1473-3099(06)70601-6.
- Background: PubMed 16154023Burton PR, Tobin MD, Hopper JL. Key concepts in genetic epidemiology. Lancet. 2005 Sep 10-16;366(9489):941-51. doi: 10.1016/S0140-6736(05)67322-9.
- Background: PubMed 10608786Buxton Bridges C, Katz JM, Seto WH, Chan PK, Tsang D, Ho W, Mak KH, Lim W, Tam JS, Clarke M, Williams SG, Mounts AW, Bresee JS, Conn LA, Rowe T, Hu-Primmer J, Abernathy RA, Lu X, Cox NJ, Fukuda K. Risk of influenza A (H5N1) infection among health care workers exposed to patients with influenza A (H5N1), Hong Kong. J Infect Dis. 2000 Jan;181(1):344-8. doi: 10.1086/315213.
- Background: PubMed 16369534Chan VS, Chan KY, Chen Y, Poon LL, Cheung AN, Zheng B, Chan KH, Mak W, Ngan HY, Xu X, Screaton G, Tam PK, Austyn JM, Chan LC, Yip SP, Peiris M, Khoo US, Lin CL. Homozygous L-SIGN (CLEC4M) plays a protective role in SARS coronavirus infection. Nat Genet. 2006 Jan;38(1):38-46. doi: 10.1038/ng1698. Epub 2005 Dec 20.
- Background: PubMed 12642066Colhoun HM, McKeigue PM, Davey Smith G. Problems of reporting genetic associations with complex outcomes. Lancet. 2003 Mar 8;361(9360):865-72. doi: 10.1016/s0140-6736(03)12715-8.
- Background: PubMed 3102964Densen P, Weiler JM, Griffiss JM, Hoffmann LG. Familial properdin deficiency and fatal meningococcemia. Correction of the bactericidal defect by vaccination. N Engl J Med. 1987 Apr 9;316(15):922-6. doi: 10.1056/NEJM198704093161506. No abstract available.
- Background: PubMed 14500706Gagneux P, Cheriyan M, Hurtado-Ziola N, van der Linden EC, Anderson D, McClure H, Varki A, Varki NM. Human-specific regulation of alpha 2-6-linked sialic acids. J Biol Chem. 2003 Nov 28;278(48):48245-50. doi: 10.1074/jbc.M309813200. Epub 2003 Sep 18.
- Background: PubMed 16757853Gilsdorf A, Boxall N, Gasimov V, Agayev I, Mammadzade F, Ursu P, Gasimov E, Brown C, Mardel S, Jankovic D, Pimentel G, Ayoub IA, Elassal EM, Salvi C, Legros D, Pessoa da Silva C, Hay A, Andraghetti R, Rodier G, Ganter B. Two clusters of human infection with influenza A/H5N1 virus in the Republic of Azerbaijan, February-March 2006. Euro Surveill. 2006;11(5):122-6.
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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.
Tawee Chotpitayasunond, Professor principal investigator
Queen Sirikit National Institute of Child Health, Bangkok, Thailand
Herawati Sudoyo, Dr. principal investigator
Eijkman Institute for Molecular Biology
Tran Hien Nguyen, Professor principal investigator
National Institute of Hygiene and Epidemiology, Hanoi, Vietnam
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 Influenza A Virus/H5N1 Subtype, run by South East Asia Infectious Disease Clinical Research Network at 1 site in Vietnam.
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 8 inclusion and 0 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 4 Nov 2010. 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 Vietnam. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01074736, which also lists 56 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 4 Nov 2010.