Contact information
Type
Scientific
Primary contact
Dr Peter Howarth
ORCID ID
Contact details
IIR (RCMB) MP810
Level F
South Block
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
-
P.H.Howarth@soton.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
BRU 3.1, Sponsor no. RHM MED 0879
Study information
Scientific title
Safety and efficacy of parenteral keratinocyte growth factor (KGF) in moderate asthma subjects: a double-blind placebo-controlled randomised parallel group trial
Acronym
Study hypothesis
That restoration of the bronchial epithelial barrier in asthma by treatment with KGF will reduce the responsiveness of the lungs to bronchoconstrictor agents, reduce airway inflammation and improve clinical disease expression.
Ethics approval
Pending as of 17/06/2009 from the Southampton and South West Hampshire Local Research Ethics Committee (LREC)
Study design
Randomised double blind placebo controlled parallel group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Asthma
Intervention
The study population will be screened including medical history, examination, spirometry, diary card monitoring, exhaled nitric oxide measurement, skinprick testing, mannitol and metacholine provocation tests and baseline bronchoscopy. The intervention group will receive intravenous keratinocyte growth factor (KGF) in a 'collapsed dose' regime, at a dose of 180 µg/kg, given as an infusion on days 0 and day 11 of the trial. The control group will receive saline infusions. In between the doses and following the second doses the subjects will have further provocation tests and a further bronchoscopy. Subjects will be followed up for 36 days following the initial dose of the study drug/placebo.
Intervention type
Drug
Phase
Not Applicable
Drug names
Keratinocyte growth factor
Primary outcome measures
Change in provocative concentration in mannitol causing a 20% fall in FEV1 (PC20), measured in screening and on days 3, 14, 18 and 36
Secondary outcome measures
1. Asthma symptoms, assessed continuously during the trial
2. Short acting B-2-agonist usage, assessed continuously during the trial
3. Lung function (home peak expiratory flow rate [PEFR] recording and clinic FEV1 and forced vital capacity [FVC])
4. Change in PC20 methacholine, assessed in screening and on day 17 and 35
5. Change in exhaled NO (eNO), assessed in screening and on days 3, 14, 18 and 36
6. Expression of ZO-1 and occludin in the bronchial epithelium
7. Bronchial biopsy epithelial integrity
8. Mucosal cellular inflammation (eosinophils, mast cells, neutrophils T-cells), assessed from bronchocopy in screening and on day 21
9. Epithelial activation markers (interleukin-8 [IL-8], regulated upon activation, normal T cell expressed and secreted [RANTES], macrophage inflammatory protein-1alpha [MIP-1a], macrophage chemotactic protein-1 [MCP-1], transforming growth factor alpha [TGF-a], epidermal growth factor receptor [EGFR]), assessed from bronchocopy in screening and on day 21
10. Safety readouts (clinical adverse event reporting), assessed continuously
11. Safety-related histochemistry readouts (epithelial Ki 61), assessed continuously
Overall trial start date
01/08/2009
Overall trial end date
01/11/2009
Reason abandoned
Eligibility
Participant inclusion criteria
1. Aged 18 - 50 years, either gender
2. Confirmed diagnosis of asthma for greater than 1 year as defined by British Thoracic Society (BTS) guidelines, requiring treatment with high dose inhaled corticosteroids in combination with long acting beta-2-agonists, with persisting symptoms requiring use of short-acting beta agonist therapy greater than 3 x/week
3. Lifelong non-smoker
4. Forced expiratory volume in one second (FEV1) greater than 40%
5. Subject must understand the procedures of the study and agree to participation in the study by providing written informed consent
6. Subject considered fit enough to undergo lung function testing including provocation tests, and bronchoscopy
7. Subject must not be participating in another clinical trial or have done so within the last 12 weeks
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
20
Participant exclusion criteria
1. Pregnancy (where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotrophin [hCG] laboratory test greater than 5 mIU/ml), an intention to become pregnant or breast-feeding (lactating)
2. Subjects with active lung disease other than asthma
3. Significant medical (cardiopulmonary, neurological, renal, endocrine, gastrointestinal, psychiatric, hepatic or haematological) co-morbidity which in the view of the investigator could impact on the interpretation of results or participation in the trial, or which is uncontrolled with standard treatment
4. Current participation in another clinical trial or previous participation within the last 12 weeks
5. Alcohol or active drug abuse
6. Ongoing allergen desensitisation therapy
7. Regular use of sedatives, hypnotics, tranquilisers
8. Cancer or previous history of cancer
9. Inability to understand directions for dosing and study assessment
10. Inability to be contacted in case of emergency
Recruitment start date
01/08/2009
Recruitment end date
01/11/2009
Locations
Countries of recruitment
United Kingdom
Trial participating centre
IIR (RCMB) MP810
Southampton
SO16 6YD
United Kingdom
Sponsor information
Organisation
Southampton University Hospitals NHS Trust (UK)
Sponsor details
Research and Development
Duthie Building (Trust) MP138
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
+44 (0)2380 794 149
angela.jackson@suht.swest.nhs.uk
Sponsor type
Government
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Southampton General Hospital (UK) - Internal funding by Biomedical Research Unit
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary