Treatment With AKL1 in Obstructive Airways Disease (The TAKL Study)

Asthma Clinical Trial

— TAKL  

Official title:

An Investigation of the Safety and Efficacy of Oral AKL1 in Patients Diagnosed With Obstructive Lung Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00920127
• Other study ID #: 32227/0001/001
• Secondary ID: EudraCT: 2222 -
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• First received: June 12, 2009
• Last updated: August 4, 2011
• Start date: June 2009
• Est. completion date: February 2012

Study information

• Verified date: August 2011
• Source: University of East Anglia
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

Obstructive airways disease is a very common condition. This condition includes patients with asthma, chronic obstructive pulmonary disease (COPD), emphysema or chronic bronchitis. Some patients with obstructive airways disease have problems with long term breathlessness, wheeze and cough with or without sputum production. Currently the researchers give treatments - usually inhalers - which are designed to open the airways and reduce the breathlessness and wheeze. Despite these available treatments many patients still have continuing symptoms.

Anecdotal clinical evidence suggested that a herbal remedy (called AKL1) has beneficial effects in respiratory conditions, with patients diagnosed as having both asthma and COPD reporting reduced symptoms including breathlessness and cough and reduced frequency of attacks.The purpose of this study is to confirm whether AKL1 does indeed have a meaningful benefit to patients with obstructive airways disease. The researchers will mainly be measuring any effect of AKL by assessing any change in trial subjects' coughs, using a questionnaire, but the researchers will also looking at breathing tests, walking tests, blood and sputum tests.

Description:

The outcomes of care for obstructive airways disease in the UK and other countries fail to meet guideline targets, with high levels of avoidable morbidity and avoidable mortality. Obstructive lung disease is an encompassing term for a condition that includes patients with a reversible (asthma) or non reversible (chronic obstructive pulmonary disease) component to their lung function.

AKL1 is a novel pharmaceutical agent derived from a combination of botanical products developed as a treatment for obstructive lung disease (asthma and COPD). The botanical product contains a synthetically-derived phytochemical component of Picrorrhiza kurroa, apocynin, together with standardized extracts of Picrorrhiza kurroa, Zingiber officinale and Ginkgo biloba that have previously been marketed as a health food supplements. Recent evidence suggests that Ginkgo biloba reduces inflammatory (protein kinase C positive ie eosinophils and neutrophils) cells in induced sputum which given in addition to inhaled corticosteroids to asthmatic patients. Anecdotal clinical evidence suggests that the botanical product has significant activity in respiratory conditions, with patients diagnosed as having obstructive lung disease (asthma and COPD) reporting reduced symptoms including breathlessness and cough, reduced frequency of attacks, reduced dependence on bronchodilators and ability to reduce inhaled corticosteroids dose.

We have completed a pilot study investigating the efficacy and safety of AKL1 as 'add-on' therapy for adult patients diagnosed as having obstructive lung disease whose symptoms remained uncontrolled on standard medication. Whilst there was no significant differences in lung function, there were trends to clinical improvements in the patient-centered outcomes e.g. cough, health status and exacerbation frequency. Hence a larger adequately powered study is needed to investigate these outcomes further.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 164
• Est. completion date: February 2012
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Males or females, aged between 18 to 80 years, inclusive

• The patient has received verbal and written study information, all questions have been answered satisfactorily and a consent form has been personally signed and dated by the patient and the investigator

• A diagnosis of obstructive lung disease (with reference to the - International Primary Care Respiratory Group (IPCRG) Guidelines)(4). This being evidenced as a post bronchodilator ratio of FEV1/FVC < 0.7 at Visit 1 or 2 The patient has a post bronchodilator FEV1 of greater than 40% and less than 80% at Visit 1 or 2

• Patients have a history of regular sputum production (> 3 days per week)

• LCQ score of <17 (higher score indicates improvement).

• A MRC dyspnoea score of 3 or more

• Females must be post menopausal (> 1 year), surgically sterilised or using adequate hormonal contraception, intrauterine device), not breast feeding and have a negative serum pregnancy test

• The patient must have a satisfactory health with the exception of obstructive lung disease as determined by the investigator on the basis of medical history and physical examination

• In the Investigator's judgement, the patient is able and willing to comply with study visits and procedures (including laboratory tests, lung function tests).

• Subjects must be able to demonstrate ability to use salbutamol MDI during the screening period

Exclusion Criteria:

• The patient has currently poorly controlled disease defined as requiring a course of oral or parenteral corticosteroids or an exacerbation of their obstructive lung disease in the three months prior to Visit 2.

• The patient has had a recent change in maintenance therapy (i.e. within 6 weeks)

• Maintenance oral corticosteroid treatment or use of unlicensed doses of inhaled corticosteroid medication (>2000mcg beclomethasone diproprionate/ day or equivalent)

• The patient has seasonal disease alone

• The patient has any known laboratory abnormality, which in the opinion of the investigator, would contraindicate study participation, including, aspartate aminotransferase (AST) or alanine aminotransferase (ALT)greater/equal to 1.5 x upper limit of normal (ULN) or creatinine > 1.5 mg/dL

• The patient is unable to discontinue short-acting beta-2-adrenergic agonists for at least 4 hours, long-acting beta agonists (12 hours) and tiotropium (24 hours) prior to Visit 2 (Week 0)

• The patient has chronic heart failure class III or IV (New York Heart Association) or a recent (less than six months) history of stroke, transient ischemic attack or myocardial infarction

• The patient is not able to follow study procedures (e.g., language problems, psychological disorders) or is considered to be non-compliant according to the investigator.

• The patient has a history of known alcohol or substance abuse (excluding cigarettes) within the one-year prior to Visit 1

• The patient has an active malignancy of any type or history of a malignancy (with the exception of patients with malignancy surgically removed with no evidence of recurrence within five years before enrolment, and patients with history of treated basal cell carcinoma)

• The patient has any other severe or acute or chronic medical or psychiatric conditions that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. Subjects with a malignancy and who are currently undergoing radiation therapy or have had chemotherapy within 5 years.

• The patient has difficulty swallowing capsules or tablets, dysphagia or is unable to tolerate oral medication

• The patient has been previously admitted to the study or currently participating or have recently participated in another trial with an investigational drug within 90 days of the start of this study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma
• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Obstructive Lung Disease
• Pulmonary Disease, Chronic Obstructive

Intervention

Dietary Supplement:
• AKL1
Each dose of AKL1 or placebo will consist of two capsules which will be swallowed twice daily for 8 weeks. The morning dose of study medication should be taken at approximately the same time each morning between 7:00 am and 10:00 am and should consist of two 500 mg capsules and then repeated between 7.00 pm and 10 pm.

Locations

Country	Name	City	State
United Kingdom	University of East Anglia	Norwich	Norfolk

Sponsors (1)

Lead Sponsor	Collaborator
University of East Anglia

Country where clinical trial is conducted

United Kingdom, 

References & Publications (11)

Birring SS, Prudon B, Carr AJ, Singh SJ, Morgan MD, Pavord ID. Development of a symptom specific health status measure for patients with chronic cough: Leicester Cough Questionnaire (LCQ). Thorax. 2003 Apr;58(4):339-43. — View Citation

Cote CG, Pinto-Plata V, Kasprzyk K, Dordelly LJ, Celli BR. The 6-min walk distance, peak oxygen uptake, and mortality in COPD. Chest. 2007 Dec;132(6):1778-85. Epub 2007 Oct 9. — View Citation

Dolan P. Modeling valuations for EuroQol health states. Med Care. 1997 Nov;35(11):1095-108. — View Citation

Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am Rev Respir Dis. 1992 Jun;145(6):1321-7. — View Citation

Levy ML, Fletcher M, Price DB, Hausen T, Halbert RJ, Yawn BP. International Primary Care Respiratory Group (IPCRG) Guidelines: diagnosis of respiratory diseases in primary care. Prim Care Respir J. 2006 Feb;15(1):20-34. Epub 2005 Dec 27. — View Citation

Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. — View Citation

Oostveen E, MacLeod D, Lorino H, Farré R, Hantos Z, Desager K, Marchal F; ERS Task Force on Respiratory Impedance Measurements. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur Respir J. 2003 Dec;22(6):1026-41. Review. — View Citation

Standardization of Spirometry, 1994 Update. American Thoracic Society. Am J Respir Crit Care Med. 1995 Sep;152(3):1107-36. — View Citation

Tang Y, Xu Y, Xiong S, Ni W, Chen S, Gao B, Ye T, Cao Y, Du C. The effect of Ginkgo Biloba extract on the expression of PKCalpha in the inflammatory cells and the level of IL-5 in induced sputum of asthmatic patients. J Huazhong Univ Sci Technolog Med Sci. 2007 Aug;27(4):375-80. — View Citation

Thomas M, Sheran J, Smith N, Fonseca S, Lee AJ. AKL1, a botanical mixture for the treatment of asthma: a randomised, double-blind, placebo-controlled, cross-over study. BMC Pulm Med. 2007 Mar 20;7:4. — View Citation

van der Molen T, Willemse BW, Schokker S, ten Hacken NH, Postma DS, Juniper EF. Development, validity and responsiveness of the Clinical COPD Questionnaire. Health Qual Life Outcomes. 2003 Apr 28;1:13. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The change in the Leicester Cough Questionnaire (LCQ) score		8 weeks	No
Secondary	St Georges Respiratory Questionnaire (SGRQ) score		8 weeks	No
Secondary	EQ-5D score		8 weeks	No
Secondary	Spirometry (FEV1, FVC, PEF, FEF25-75 predicted)		8 weeks	No
Secondary	Impulse Oscillometry		8 weeks	No
Secondary	Differential spontaneous sputum cell count; TNFa,IL-8, IL-10 concentration		8 weeks	No
Secondary	Modified MRC dyspnoea score		8 weeks	No
Secondary	6 minute walk		8 weeks	No
Secondary	Blood haematology and biochemistry		10 weeks	Yes
Secondary	Drug related adverse events		10 weeks	Yes