Trial record 2 of 46 for:    Open Studies | "Streptococcal Infections"

Genetic Susceptibility to Severe Streptococcal Infections

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Oxford
Sponsor:
Collaborators:
Public Health England, UK
Imperial College London
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01911572
First received: June 4, 2013
Last updated: June 13, 2014
Last verified: June 2014
  Purpose

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
Invasive Streptococcal Infection
Invasive Group A Streptococcal Disease
Invasive Group B Streptococcal Disease
Necrotising Fasciitis

Study Type: Observational
Study Design: Observational Model: Family-Based
Official Title: Genetic Susceptibility to Invasive Streptococcal Disease

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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 - http://www.uk10k.org/). 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.


Estimated Enrollment: 200
Study Start Date: December 2013
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Survivors
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.

  Eligibility

Genders Eligible for Study:   Both
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.

Criteria

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.

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01911572

Contacts
Contact: Tom Parks, BA MB BChir MRCP DTM&H 07795082724 tomparks@well.ox.ac.uk

Locations
United Kingdom
University of Oxford Wellcome Trust Centre for Human Genetics Recruiting
Oxford, Oxon, United Kingdom, OX3 7BN
Contact: Tom Parks, BA MB BChir MRCP DTM&H    +447795082724    tomparks@well.ox.ac.uk   
Principal Investigator: Tom Parks, BA MB BChir MRCP         
Sponsors and Collaborators
University of Oxford
Public Health England, UK
Imperial College London
Investigators
Principal Investigator: Tom Parks, BA MB BChir MRCP DTM&H University of Oxford
  More Information

Additional Information:
No publications provided

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01911572     History of Changes
Other Study ID Numbers: GENIGASUK
Study First Received: June 4, 2013
Last Updated: June 13, 2014
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Oxford:
Streptococcus species
Streptococcus pyogenes
Streptococcus agalactiae
Necrotising fasciitis
Sepsis

Additional relevant MeSH terms:
Streptococcal Infections
Disease Susceptibility
Fasciitis
Fasciitis, Necrotizing
Genetic Predisposition to Disease
Disease Attributes
Pathologic Processes
Musculoskeletal Diseases
Gram-Positive Bacterial Infections
Bacterial Infections
Skin Diseases, Bacterial

ClinicalTrials.gov processed this record on September 11, 2014