Immunogenicity of Pneumococcal Vaccines in Ataxia-telangiectasia Patients

• ClinicalTrials.gov Identifier: NCT01075438
• Recruitment Status: Unknown
• First Posted: February 25, 2010
• Last Update Posted: March 16, 2010
• Sponsor: Sheba Medical Center
• Information provided by: Sheba Medical Center

Study Description

Brief Summary:

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 or disease	Intervention/treatment
Ataxia Telangiectasia	Biological: Prevenar® (7-valent pneumococcal conjugate vaccine); Biological: Pneumovax® (pneumococcal polysaccharide vaccine)

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.

Study Design

• Study Type: Observational
• Estimated Enrollment: 20 participants
• 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
• Study Start Date: March 2010
• Estimated Primary Completion Date: February 2011
• Estimated Study Completion Date: February 2011

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. 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 ]

Biospecimen Retention:   Samples Without DNA

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

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 25 Years (Child, Adult)
• Sexes Eligible for Study: All
• 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

Contacts

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

Locations

Israel

Chaim Sheba Medical Center

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

• Responsible Party: Galia Barkai, Sheba Medical Center
• ClinicalTrials.gov Identifier: NCT01075438
• Other Study ID Numbers: SHEBA-09-7444-GB-CTIL
• First Posted: February 25, 2010
• Last Update Posted: March 16, 2010
• Last Verified: March 2010

Keywords provided by Sheba Medical Center:

ataxia telangiectasia; Pneumococcal Vaccines

Additional relevant MeSH terms:

Ataxia; Cerebellar Ataxia; Ataxia Telangiectasia; Telangiectasis; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Spinocerebellar Ataxias; Neurocutaneous Syndromes; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine; Immunologic Factors; Physiological Effects of Drugs