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Trial record 14 of 17 for:    Necrotizing Fascitis

Genetic Susceptibility to Severe Streptococcal Infections

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01911572
Recruitment Status : Unknown
Verified May 2018 by University of Oxford.
Recruitment status was:  Active, not recruiting
First Posted : July 30, 2013
Last Update Posted : May 18, 2018
Public Health England
Imperial College London
Information provided by (Responsible Party):
University of Oxford

Brief Summary:

Invasive bacterial infection is a dangerous but relatively uncommon disease where bacteria spread deep into the body causing diseases like blood poisoning ('bacteraemia'), pneumonia, meningitis and others. The various bacteria of the streptococcus family are an important cause, often leading patients to require intensive care despite which, for some strains, one in five patients die. One notable form is called necrotising fasciitis, a condition where bacteria rapidly spreads through and destroys the layers of tissue just under the skin.

As individuals vary greatly in their risk of developing such serious infections, investigating how the genome, the inherited blueprint of our bodies, of these patients differs from that of healthy volunteers can help to explain why the disease develops in some and not others. For some streptococcal bacteria such as Streptococcus pneumoniae this approach is already proving successful; for others such as the "Group A" strain (Streptococcus pyogenes) it has yet to be explored but carries excellent potential.

The investigators have secured the support of the Lee Spark Necrotising Fasciitis Foundation to recruit from their membership survivors of streptococcal infections and some of their family members. The investigators will also ask infection specialists from NHS hospitals to invite patients they have looked after. The investigators also have a small existing collection. Taking part would involve registering information on a website, discussing the study on the telephone and then providing us with a sample of saliva from which the investigators can isolate DNA. The investigators would prepare the sample for analysis of the genome and compare the patients with both their family and an existing reference collection from healthy volunteers using technology that reads the DNA code.

Our study will be a first key step in renewing efforts to understand the determinants of invasive streptococcal infection, which is important for developing better treatments and vaccines.

Condition or disease
Invasive Streptococcal Infection Invasive Group A Streptococcal Disease Invasive Group B Streptococcal Disease Necrotising Fasciitis

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Family-Based
Time Perspective: Other
Official Title: Genetic Susceptibility to Invasive Streptococcal Disease
Study Start Date : December 2013
Actual Primary Completion Date : December 2017
Estimated Study Completion Date : December 2019

Individuals who have previously experienced an episode of invasive streptococcal infection or necrotising fasciitis.
Family members
Parents of those survivors aged less than forty years without risk factors for streptococcal disease (forming mother-father-child trios), or first and second degree relatives of survivors from a family in which two or more individuals have been affected.

Primary Outcome Measures :
  1. Number of genetic variants at which cases of invasive streptococcal infection (as defined in inclusion criteria 1) differ from their family members (inclusion criteria 2-4) [ Time Frame: The outcome is measured once by genetic testing using a sample collected on enrolment ('baseline'). There is no follow-up period. ]
    This is an observational study comparing genetic data from cases (inclusion criteria 1) vs unaffected family members (inclusion criteria 2-4) and publically available genetic data from health volunteers in existing reference databases (e.g. UK10K - The case's illness (as defined in inclusion criteria 1) may have occurred anytime between 1st January 1980 and enrolment. The outcome is measured by genetic testing using a sample collected on enrolment. There is no follow-up period.

Biospecimen Retention:   Samples With DNA
Primarily we will collect saliva from which DNA will be isolated. Secondly, from a subset of individuals, we will request follow-up blood samples from which we will extract RNA and separate leukocytes for studies of function.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Participants will be identified through an invitation sent to the Lee Spark Necrotising Fasciitis Foundation and by infection specialists at NHS hospitals who will invite patients whose care they have been directly involved in. In addition, a small collection of existing samples held at Imperial College London will be used.

Participants for the genetics study are divided into cases/survivors and family members (relatives and parents).

To participate as a survivor, the individual must meet criteria 1A. Their illness can have occurred anytime from birth up until enrolment, providing it happened after 1st January 1980. Family members can only take part if invited to do so by the survivor from their family at the request of the research team.

In families in which two or more survivors are identified, all the remaining first- and second-degree relatives of the survivors will be eligible to participate. The recruitment team subdivide those relatives on enrolment into healthy (Criteria 2) or intermediate (Criteria 3) phenotype.

In families in which there is only a single survivor, the recruitment team will assess whether the survivor meets criteria 1B. If so the parents of that survivor are eligible to participate if they have a healthy phenotype (Criteria 4).

Inclusion Criteria:

  1. Cases/Survivors

    A. All Cases (survivors in pedigree, trio or as simplex case; existing serum samples from Imperial College London collection)

    • Either of:

      • Isolation of Streptococcus species from a normally sterile site (e.g. blood, joint fluid, etc.) during an acute illness since 1st January 1980
      • Severe clinical presentation - streptococcal toxic shock, necrotising fasciitis, pneumonia, puerperal sepsis, meningitis - since 1st January 1980 plus concurrent Streptococcus species isolated from non-sterile site (e.g. abscess, wound swab, pus)
    • And:

      • Admitted to an NHS hospital in England or Wales or Northern Ireland

    B. Trio case (survivor in trio)

    • All of:

      • Meets criteria for 1A
      • Less than 40 years of age at the time of illness
      • None of at the time of the illness: heart disease, diabetes mellitus, cancer, steroid use, chronic lung disease, immunocompromise, intravenous drug use and alcoholism
    • Plus one of:

      • More than one episode of illness meeting criteria for 1A
      • Admission to high dependency or intensive care unit
      • Requirement for surgical procedure (including drainage of abscess or collection)
    • And:

      • Both parents alive at time of recruitment
  2. Unaffected phenotype family member in multi-case pedigree

    • All of:

      • Biological first or second degree relative of a survivor meeting criteria 1A in a family in which two or more members meet those criteria
      • None of: severe streptococcal illness requiring hospital illness, recurrent tonsillitis or recurrent impetigo (recurrent is defined as more than one episode in two consecutive years)
  3. Intermediate phenotype family member in multi-case pedigree

    • All of:

      • Biological first or second degree relative of a survivor meeting criteria 1A in a family in which two or more members meet those criteria
      • History of severe bacterial illness requiring hospital admission, recurrent tonsillitis or recurrent impetigo (recurrent is defined as more than one episode in two consecutive years)
  4. Parent in mother-father-child trio

    • All of:

      • Biological parent of case meeting criteria for 1B
      • None of: severe bacterial illness requiring hospital admission, recurrent tonsillitis or recurrent impetigo (recurrent is defined as more than one episode in two consecutive years)

Exclusion Criteria:

1. Adults (age > 16 years) unable to consent for themselves.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01911572

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United Kingdom
University of Oxford Wellcome Trust Centre for Human Genetics
Oxford, Oxon, United Kingdom, OX3 7BN
Sponsors and Collaborators
University of Oxford
Public Health England
Imperial College London
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Principal Investigator: Tom Parks, BA MB BChir MRCP DTM&H University of Oxford

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Responsible Party: University of Oxford Identifier: NCT01911572    
Other Study ID Numbers: GENIGASUK
First Posted: July 30, 2013    Key Record Dates
Last Update Posted: May 18, 2018
Last Verified: May 2018
Keywords provided by University of Oxford:
Streptococcus species
Streptococcus pyogenes
Streptococcus agalactiae
Necrotising fasciitis
Additional relevant MeSH terms:
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Fasciitis, Necrotizing
Streptococcal Infections
Genetic Predisposition to Disease
Disease Susceptibility
Disease Attributes
Pathologic Processes
Musculoskeletal Diseases
Gram-Positive Bacterial Infections
Bacterial Infections
Skin Diseases, Bacterial