Immunogenicity of Pneumococcal Vaccines in Ataxia-telangiectasia Patients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2010 by Sheba Medical Center.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
Sheba Medical Center
ClinicalTrials.gov Identifier:
NCT01075438
First received: February 24, 2010
Last updated: March 15, 2010
Last verified: March 2010
  Purpose

Ataxia-telangiectasia (AT) is a rare genetic disorder characterized by gait disorders, neuromotor dysfunction, eye abnormalities and immune deficiency. AT patients are vulnerable to cancer and infection and usually die during their 2nd or 3rd decade due to these complications. The main cause of death is respiratory infections because these patients are known to have severe type of immunodeficiency. Consequently, pneumonia is the most common infection seen in AT patients, and is usually caused by S. pneumoniae. Therefore, a routine schedule of pneumococcal vaccine is highly recommended in AT cases where immunoglobulin replacement therapy was not already initiated.

Until recently, AT patients were immunized with the pneumococcal polysaccharide vaccine (PPV23, Pneumovax® Aventis Pasteur MSD). However, data have shown that they do not respond well to these vaccines. Recently, the Israeli Ministry of Health has approved the pneumococcal 7-valent conjugate vaccine (PCV7, Prevenar®, Wyeth Lederle) for AT patients of all ages. This conjugate vaccine is known to stimulate the immune system through a different mechanism and the response is expected to be higher. The approved Israeli schedule for immunization of AT patients includes children older than 2 years that are entitled to receive 2 doses of PCV7 (8 weeks apart) boosted by PPV23, eight weeks after the second dose of PCV7. Assessment of the antibody response of such pneumococcal vaccination protocol in AT patients has never been performed.

The "Safra" Children's Hospital is the national multi-disciplinary center caring for AT patients. Approximately 50 patients from all over the country (including Jewish, Druze, Bedouin and other Muslim patients - 3 of whom are Palestinians) are followed in the clinic on a monthly basis.

Approximately 20 AT patients are not receiving IVIG replacement therapy, therefore are entitled to receive pneumococcal vaccination as stated above (mean age 10.6, 3 -23 years, 3 less than 5 years)

The aim of this study is to evaluate the responsiveness, determined by specific antibody production, of AT patients receiving this new vaccine protocol.


Condition Intervention
Ataxia Telangiectasia
Biological: Prevenar® (7-valent pneumococcal conjugate vaccine)
Biological: Pneumovax® (pneumococcal polysaccharide vaccine)

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Descriptive Immunogenicity of 2 Doses of Pneumococcal 7-valent Conjugate Vaccine (Prevenar®, Wyeth Lederle) Followed by Pneumococcal Polysaccharide Vaccine (Pneumovax® Aventis Pasteur MSD) in Ataxia-telangiectasia Patients

Resource links provided by NLM:


Further study details as provided by Sheba Medical Center:

Primary Outcome Measures:
  • Primary end point will be levels of antibodies against 13 serotypes of streptococcus pneumoniae following vaccination with 2 doses of PCV7 and 1 dose of PPV23. All endpoints will include both ELISA and OPA antibodies. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Serum for specific anti-pneumococcal antibody levels and Immunoglobulin levels.


Estimated Enrollment: 20
Study Start Date: March 2010
Estimated Study Completion Date: February 2011
Estimated Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: Prevenar® (7-valent pneumococcal conjugate vaccine)

    Pneumococcal vaccines (conjugate and polysaccharide)

    Intramuscular Injections: 2 doses of 7-valent pneumococcal conjugate vaccine 8 weeks apart and 1 dose of pneumococcal polysaccharide vaccine 8 weeks later

    Other Names:
    • Prevenar®, Wyeth
    • Pneumovax® Aventis Pasteur MSD
    Biological: Pneumovax® (pneumococcal polysaccharide vaccine)

    Pneumococcal vaccines (conjugate and polysaccharide)

    Intramuscular Injections: 2 doses of 7-valent pneumococcal conjugate vaccine 8 weeks apart and 1 dose of pneumococcal polysaccharide vaccine 8 weeks later

Detailed Description:

Ataxia-telangiectasia (AT) is a rare progressive neurodegenerative autosomal recessive disorder characterized by cerebellar ataxia, neuromotor dysfunction, oculocutaneous telangiectasia and immunodeficiency. AT patients are vulnerable to cancer and infection and usually die during their 2nd or 3rd decade due to these complications. Life expectancy does not correlate well with severity of neurological impairment. The main cause of death is respiratory infections because these patients are known to have severe type of immunodeficiency. The immunodeficiency of AT patient consists of both humoral defect (immunoglobulin deficiency and reduced response to polysaccharide antigens) and cell-mediated defect (reduced lymphocytes number and function). Consequently, pneumonia is the most common infection seen in AT patients, and is usually caused by S. pneumoniae. Therefore, a routine schedule of pneumococcal vaccine is highly recommended in AT cases where immunoglobulin replacement therapy was not already initiated.

Until recently, AT patients were immunized with the pneumococcal polysaccharide vaccine (PPV23, Pneumovax® Aventis Pasteur MSD). However, data have shown that they do not respond well to these vaccine mainly because of their reduced response to polysaccharide stimulation. Recently, the Israeli Ministry of Health has approved the pneumococcal 7-valent conjugate vaccine (PCV7, Prevenar®, Wyeth Lederle) for AT patients of all ages. In contrast to polysaccharide vaccines, this conjugate vaccine is known to stimulate the immune system through T-cell dependent mechanism, and therefore the response is expected to be higher. The approved Israeli schedule for immunization of AT patients includes children older than 2 years that are entitled to receive 2 doses of PCV7 (8 weeks apart) boosted by PPV23, eight weeks after the second dose of PCV7. Assessment of the immunogenicity of such pneumococcal vaccination protocol in AT patients has never been performed.

The "Safra" Children's Hospital is the national multi-disciplinary center caring for AT patients. Approximately 50 patients from all over the country (including Jewish, Druze, Bedouin and other Muslim patients - 3 of whom are Palestinians) are followed in the clinic on a monthly basis.

Approximately 20 AT patients are not receiving IVIG replacement therapy, therefore are entitled to receive pneumococcal vaccination as stated above (mean age 10.6, 3 -23 years, 3 less than 5 years.

The aim of this study is to evaluate the responsiveness, determined by specific antibody production, of AT patients receiving the new vaccine protocol that was recently approved to use by the Israeli Ministry of Health.

  Eligibility

Ages Eligible for Study:   2 Years to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Ataxia Telangiectasia patients, not cuurntly on replacement Immunoglobulin G therapy

Criteria

Inclusion Criteria:

  1. AT patients attending the national AT clinic
  2. 2+ years of age
  3. Agree to join this study

Exclusion Criteria:

  1. Patients on regular immunoglobulin replacement therapy (other patients who are not on replacement therapy but have received IVIG 3 months or less before the beginning of the study)
  2. Current infection
  3. Previous serious adverse reactions to vaccination
  4. Administration of other vaccines within 4 weeks before administration of study vaccine or plan for vaccination 26 weeks following the first vaccine (PCV7)
  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: NCT01075438

Contacts
Contact: Galia Barkai, MD 972-3-530-5978 Galia.Barkai@sheba.health.gov.il

Locations
Israel
Chaim Sheba Medical Center Not yet recruiting
Tel Hashomer, Israel, 52621
Contact: Galia Barkai, MD    972-3-5305978    Galia.Barkai@sheba.health.gov.il   
Principal Investigator: Galia Barkai, MD         
Sponsors and Collaborators
Sheba Medical Center
  More Information

No publications provided

Responsible Party: Galia Barkai, Sheba Medical Center
ClinicalTrials.gov Identifier: NCT01075438     History of Changes
Other Study ID Numbers: SHEBA-09-7444-GB-CTIL
Study First Received: February 24, 2010
Last Updated: March 15, 2010
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Sheba Medical Center:
ataxia telangiectasia
Pneumococcal Vaccines

Additional relevant MeSH terms:
Ataxia
Ataxia Telangiectasia
Cerebellar Ataxia
Spinocerebellar Ataxias
Telangiectasis
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebellar Diseases
DNA Repair-Deficiency Disorders
Dyskinesias
Genetic Diseases, Inborn
Immune System Diseases
Immunologic Deficiency Syndromes
Metabolic Diseases
Nervous System Diseases
Neurocutaneous Syndromes
Neurologic Manifestations
Signs and Symptoms
Vascular Diseases

ClinicalTrials.gov processed this record on October 23, 2014