Anti-inflammatory and antimicrobial effects of nicotinamide in bronchiectasis

Phase 1

• Conditions: non-cystic fibrosis bronchiectasis; Respiratory - Other respiratory disorders / diseases

• Registration Number: ACTRN12615000359538
• Lead Sponsor: Dr Conroy Wong

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-04-20
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: ot yet recruiting
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1.Aged greater than or equal to 18 and less than or equal to 90 years
2.Able to provide written informed consent
3.Able to provide spontaneous sputum sample at visit 2 (week 0).
4.High-resolution CT (HRCT) diagnosis of bronchiectasis, CT scan performed within the past 2 years
5.Clinically stable during baseline period, which is 4 weeks prior to randomisation; (as defined by the absence of clinical worsening beyond normal daily variation, with no need for increasing habitual medications or taking antibiotics or prednisone and stable spirometry)
6.History of at least one pulmonary exacerbation requiring antibiotic treatment in the past 12 months. Patients with asthma and COPD will be included if the primary diagnosis is bronchiectasis.

Exclusion Criteria

1.Patients with significant abnormal liver function (AST/ALT greater than 1.5 x upper limit of normal range) or liver cirrhosis
2.Patients taking isoniazid (interaction with nicotinamide)
3.Patients taking sodium valproate or any other known histone deacetylase inhibitor.
4.Patients taking vitamin B3, niacin or nicotinamide supplements within 1 week of commencing study drug.
5.Continuous antibiotic therapy (greater than 3 months)
6.Long term macrolide treatment (greater than or equal to 3 months) in the past 6 months
7.Patients taking continuous oral corticosteroids (greater than 6 weeks) or immunosuppressive agents (e.g. azathioprine, methotrexate, cyclophosphamide).
8.Bronchiectasis exacerbation or respiratory infection requiring oral or intravenous antibiotic or steroid treatment within 4 weeks of commencing study drug.
9.Patients with a history of non-adherence with medications
10.Patient with significant medical conditions other than bronchiectasis
-A significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary aim of feasibility study: To assess whether high dose nicotinamide treatment has anti-inflammatory effects in the airways of patients with bronchiectasis.<br>Primary end point: Measured using sputum tests to determine levels of Sputum cytokines TNFa, IL-1ß, IL-6 and IL-8[8 weeks]

Secondary Outcome Measures

Name	Time	Method
To assess the effects of nicotinamide on systemic inflammation and determine whether nicotinamide has antimicrobial effects. <br>Measured using blood tests to determine <br>Plasma cytokines TNFa, IL-1ß, IL-6 and IL-8<br>Plasma concentration of nicotinamide<br>Sputum and plasma GM-CSF <br>Sputum cathelicidin LL-37, lactoferrin<br>Plasma CRP <br>Blood neutrophil counts<br>[8 weeks];To assess adherence, tolerability and safety of high dose nicotinamide treatment.<br>Measured using:<br>Lung function (FEV1, FVC),<br>Diary cards to record symptom severity <br>Health-related quality of life (St George’s Respiratory Questionnaire, Quality of Life Questionnaire-Bronchiectasis)<br>Recording of Adverse event and exacerbations<br>[8 weeks]