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TNF-Alpha Directed Therapy in Asthma

This study has been completed.
Sponsor:
Information provided by:
Imperial College London
ClinicalTrials.gov Identifier:
NCT00278083
First received: January 17, 2006
Last updated: NA
Last verified: January 2006
History: No changes posted
  Purpose

This trial is a randomised, single-center, placebo-controlled, double blind, parallel group study in patients with asthma symptomatic on inhaled steroids.

This trial will examine the efficacy and safety of 5 mg/kg doses of infliximab in patients with inhaled corticosteroid-dependent asthma. The primary objective of this study is to obtain pharmacological evidence for a role of the pro-inflammatory cytokine TNF-alpha in patients with asthma symptomatic on inhaled steroids and to evaluate the safety and tolerability of repeated intravenous administration of infliximab.


Condition Intervention Phase
Asthma
Drug: Study drug administration
Procedure: Tuberculin intradermal skin test
Procedure: Lung function test for FEV1
Procedure: Asthma symptom scores diary
Procedure: Quality of life diary
Procedure: Breath nitric oxide
Procedure: Breath condensate
Procedure: Sputum induction
Procedure: Blood sampling
Procedure: Urinalysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomised, Double Blind, Placebo-Controlled, Parallel Group Pilot Study to Determine the Effect of REMICADE on Safety, Efficacy and Biomarkers of Inflammation in Patients With Asthma Receiving Inhaled Corticosteroids

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Change from baseline (prior to visit 4: days –7 to –1) to week 8 (prior to visit 8: days 49-56) in mean morning PEFR from clinical diaries:
  • The morning PEFR for a 7 day period (week 7 to 8) will be compared to the 7 day period prior to first administration (days –7 to –1).

Secondary Outcome Measures:
  • 1. Evening PEFR
  • 2. FEV1 from clinical diaries and on study visits
  • 3. Diurnal variation in PEFR
  • 4. Symptoms score
  • 5. Short-acting beta2-agonist usage = rescue salbutamol
  • 6. Exacerbation’s and episode-free days
  • 7. Quality of life (St. George’s Respiratory Questionnaire)
  • 8. Exhaled breath NO and breath condensates
  • 9. Sputum levels of IL-8, TNF-alpha and eotaxin (in supernatant) and differential white cell count
  • 10. Peripheral blood eosinophil count, and total IgE
  • 11. Expression of mRNA related to inflammation in peripheral blood

Estimated Enrollment: 40
Study Start Date: October 2001
Estimated Study Completion Date: April 2004
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Have a diagnosis of moderate asthma as defined by the American Thoracic Society criteria (NIH, 1997) for > 1 year.
  2. Men and women, >/= 18 to </= 60 years of age and within 60-140% of desirable height and weight range established by the 1983 Metropolitan Life Insurance Company standards.
  3. Non-smoker for at least 1 year and less than a 10 pack year history of smoking.
  4. Screening values for haematology, biochemistry and urinalysis should be within clinically acceptable limits for this patient group.
  5. Chest radiograph at screening must show no evidence of malignancy, infection, or fibrosis. The chest radiographs should also show no apical scarring, cavitary lesions, or calcified granulomas, as evidence of past tuberculosis infections.
  6. Serological assays for hepatitis B and C must be negative for active infection.

Exclusion Criteria:

  1. Are pregnant, nursing, or planning a pregnancy within 12 months of enrolment.
  2. Diagnosis of chronic obstructive pulmonary disease, cystic fibrosis or other significant respiratory disorder (excluding asthma).
  3. Exacerbation of asthma symptoms requiring hospitalisation within the previous 12 weeks.
  4. History of clinically significant seasonal allergies will require that the patient is studied outside the allergy season.
  5. Have been previously treated with infliximab or any other therapeutic agent targeted at reducing TNF.
  6. Have been treated with any anti-CD-4 antibody.
  7. Have been treated with any investigational drug within the previous 3 months or within 5 half-lives, whichever is greater.
  8. Have previously used cyclophosphamide, nitrogen mustard, chlorambucil, or other alkylating agents.
  9. Have a history of any clinically significant adverse reaction to murine or chimeric proteins, including but not limited to allergic reactions.

11. Have had a serious infection during the previous 2 months. 12. Have a chronic or recurrent infectious disease 13. Have a history of opportunistic infections 14. Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.

15. Have a history of lymphoproliferative disease, including lymphoma 16. Currently have any known malignancy or have a history of malignancy within the previous 5 years.

17. Have had substance abuse (drug or alcohol) problem within the previous 10 years.

18. Use of restricted respiratory medication prior to screening within the following time periods: 1) oral or systemic steroids, 1 month; 2) immunosuppressant therapy, 3 months.

19. Have a history of chronic cough, haemoptysis, weight loss, or pyrexia considered suggestive of possible current tuberculosis infection.

20. Patients with current active tuberculosis (TB) or atypical mycobacterial infection or a previous history of these infections.

21. Be considered at high risk for tuberculosis according to US Centers for Disease Control and Prevention (CDC) criteria, 22. A tuberculin (purified protein derivative, PPD) intradermal skin test > 10mm induration.

23. Have demyelinating disease (multiple sclerosis), autoimmune conditions such as systemic lupus.

  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: NCT00278083

Locations
United Kingdom
NHLI Clinical Studies Unit
London, United Kingdom, SW3 6HP
Sponsors and Collaborators
Imperial College London
Investigators
Principal Investigator: Trevor T Hansel, FRCPath PhD Imperial College London
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00278083     History of Changes
Other Study ID Numbers: C0168T42
Study First Received: January 17, 2006
Last Updated: January 17, 2006
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Imperial College London:
Pharmacology
Asthma
TNF-alpha

Additional relevant MeSH terms:
Asthma
Anti-Asthmatic Agents
Bronchial Diseases
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Lung Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Respiratory Tract Diseases
Nitric Oxide
Antioxidants
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Endothelium-Dependent Relaxing Factors
Free Radical Scavengers
Gasotransmitters
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on November 20, 2014