Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000359538
Ethics application status
Approved
Date submitted
12/02/2015
Date registered
20/04/2015
Date last updated
20/04/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Anti-inflammatory and antimicrobial effects of nicotinamide in bronchiectasis
Scientific title
The effect of nicotinamide on sputum cytokines in patients with bronchiectasis
Secondary ID [1] 285576 0
Nil known
Universal Trial Number (UTN)
U1111­1163­3095
Trial acronym
NAM2 study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
non-cystic fibrosis bronchiectasis 294153 0
Condition category
Condition code
Respiratory 294428 294428 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Name: Anti-inflammatory and antimicrobial effects of nicotinamide in bronchiectasis.
Dose: 3 g daily for 1 week then 4 g daily for 6 weeks
Study Duration: 8 weeks
Mode of Administration: Oral tablet
Adherence measured by recording tablets issued and returned.
Intervention code [1] 291145 0
Treatment: Drugs
Comparator / control treatment
This is a Single centre, single-arm, pre-post, open-label study, therefore there is no comparator/control
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294255 0
Primary aim of feasibility study: To assess whether high dose nicotinamide treatment has anti-inflammatory effects in the airways of patients with bronchiectasis.
Primary end point: Measured using sputum tests to determine levels of Sputum cytokines TNFa, IL-1ß, IL-6 and IL-8
Timepoint [1] 294255 0
8 weeks
Secondary outcome [1] 312888 0
To assess the effects of nicotinamide on systemic inflammation and determine whether nicotinamide has antimicrobial effects.
Measured using blood tests to determine
Plasma cytokines TNFa, IL-1ß, IL-6 and IL-8
Plasma concentration of nicotinamide
Sputum and plasma GM-CSF
Sputum cathelicidin LL-37, lactoferrin
Plasma CRP
Blood neutrophil counts
Timepoint [1] 312888 0
8 weeks
Secondary outcome [2] 313237 0
To assess adherence, tolerability and safety of high dose nicotinamide treatment.
Measured using:
Lung function (FEV1, FVC),
Diary cards to record symptom severity
Health-related quality of life (St George’s Respiratory Questionnaire, Quality of Life Questionnaire-Bronchiectasis)
Recording of Adverse event and exacerbations
Timepoint [2] 313237 0
8 weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligible participants will be identified by the study co-ordinator and approached about study participation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Consecutive, consenting participants will be enrolled.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Single centre, single-arm, pre-post, open-label study in adult patients with stable, non-cystic bronchiectasis of 8 weeks duration.
Phase
Phase 1
Type of endpoint/s
Efficacy
Statistical methods / analysis
Descriptive statistics, including mean, standard deviation, extrema and quartiles, will be produced for each continuous outcome. Tolerability will be described using the proportion of treatment cessations due to intolerance at 8 weeks, and the histogram of final dosages. Adherence will be summarised using the proportion of unused tablets at each visit and the histogram of the number of tablets returned by each patient at each visit. Adverse events will be categorised according to standard diagnostic codes and reported in tabular form under the dosage at which they occurred.

For the primary efficacy analysis, the logarithms of the primary endpoints at weeks 2 and 8 will be fitted in a linear mixed model using the participant as random effects and the baseline value as covariate. The test statistic in this case will be the fitted intercept, which will be zero under the null hypothesis of no change. This approach is a generalisation of the ANCOVA that allows the use of repeated measures data. In practice it corresponds to comparing the average of the repeated measures at 2 and 8 weeks with baseline, accounting for the correlation between all measurements and conditioning on baseline, which improves efficiency. Should normality not be warranted for the log-transformed data, alternative generalised linear models will be sought on the basis of a visual assessment of the residuals and testing of the residuals for consistency with alternative distributions (Kolmogorov-Smirnov and Shapiro-Wilk tests). False discovery rate (FDR) control will be used to account for multiplicity.

Secondary analyses of the primary outcomes will be similar to the primary analyses but include the average true dose of nicotinamide in the preceding period of 2 or 6 weeks as a covariate. Analyses of secondary outcomes will proceed in a similar manner, with logarithmic transformations considered primarily for concentrations, counts and ratios. Inferential analyses will be carried out at a 5% significance level against two-sided alternatives. Estimates will be reported as point estimates and 95% confidence intervals.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/05/2015
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment outside Australia
Country [1] 6647 0
New Zealand
State/province [1] 6647 0
Auckland

Funding & Sponsors
Funding source category [1] 290718 0
Government body
Name [1] 290718 0
Health Research Council, New Zealand
Country [1] 290718 0
New Zealand
Primary sponsor type
Individual
Name
Dr Conroy Wong
Address
Respiratory Department
Middlemore Hospital
100 Hospital Road
Papatoetoe
Auckland 2025
Country
New Zealand
Secondary sponsor category [1] 289405 0
None
Name [1] 289405 0
Address [1] 289405 0
Country [1] 289405 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292347 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 292347 0
Health and Disability Ethics Committees
Ministry of Health
C/- MEDSAFE, Level 6, Deloitte House
10 Brandon Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 292347 0
New Zealand
Date submitted for ethics approval [1] 292347 0
Approval date [1] 292347 0
18/11/2014
Ethics approval number [1] 292347 0
14/NTA/181

Summary
Brief summary
Bronchiectasis is a chronic, debilitating disease characterised by productive cough, neutrophilic inflammation, bacterial colonisation, and repeated respiratory infections requiring antibiotics. New and innovative approaches to the treatment of airway inflammation and infection are needed. Nicotinamide, the amide derivative of vitamin B3, has anti-inflammatory and anti-oxidant effects, and has recently been shown to boost innate immunity and enhance the killing of bacteria. Several feasibility issues need to be clarified prior to undertaking a full, randomised, placebo-controlled trial of nicotinamide in patients with bronchiectasis. These include determining the effects of high dose nicotinamide on airway and systemic inflammation and antimicrobial peptides in patients with bronchiectasis. In addition, we will evaluate the tolerability and safety of high doses of nicotinamide.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 52438 0
Dr Conroy Wong
Address 52438 0
Respiratory Department
Middlemore Hospital
100 Hospital Road
Papatoetoe
Auckland 2025
Country 52438 0
New Zealand
Phone 52438 0
+64 21613307
Fax 52438 0
+64 9 2503828
Email 52438 0
cawong@middlemore.co.nz
Contact person for public queries
Name 52439 0
Dr Conroy Wong
Address 52439 0
Respiratory Department
Middlemore Hospital
100 Hospital Road
Papatoetoe
Auckland 2025
Country 52439 0
New Zealand
Phone 52439 0
+64 21613307
Fax 52439 0
+64 9 2503828
Email 52439 0
cawong@middlemore.co.nz
Contact person for scientific queries
Name 52440 0
Dr Conroy Wong
Address 52440 0
Respiratory Department
Middlemore Hospital
100 Hospital Road
Papatoetoe
Auckland 2025
Country 52440 0
New Zealand
Phone 52440 0
+64 21613307
Fax 52440 0
+64 9 2503828
Email 52440 0
cawong@middlemore.co.nz

No information has been provided regarding IPD availability


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No Supporting Document Provided


Results publications and other study-related documents

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