Condition category
Respiratory
Date applied
16/06/2009
Date assigned
07/10/2009
Last edited
24/05/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

http://www.suht.nhs.uk/home.aspx

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

Publication citations

Additional files

Editorial Notes

24/05/2016: No publications found, verifying study status with principal investigator