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Trial registered on ANZCTR


Registration number
ACTRN12611001006932
Ethics application status
Approved
Date submitted
19/09/2011
Date registered
20/09/2011
Date last updated
9/01/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
A pilot study of the tolerability and effect on smoking urges of flavoured and unflavoured nicotine inhalers that contain either pure nicotine or a nicotine salt, compared to placebo.
Scientific title
A semi-randomised placebo-controlled cross-over pilot study in heavy smokers, of flavoured and unflavoured nicotine base and nicotine lactate pressurised metered-dose formulations, comparing their tolerability and effect on smoking urges .
Secondary ID [1] 263065 0
Not applicable.
Universal Trial Number (UTN)
U1111-1124-6575
Trial acronym
INHALE-pilot
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tobacco use and dependence 270801 0
Smoking Cessation 270802 0
Condition category
Condition code
Mental Health 270994 270994 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All subjects will inhale one puff from a series of placebo and nicotine formulations during one visit to the clinic, which will last approximately 1 to 3 hours. Initially subjects will take just one puff of each formulation and rate its effects. They will wait until they feel another urge to smoke before they try one puff of the next formulation. All subjects will begin with the lowest dose of the placebo formulations (0.5% menthol), have one puff, then progress to the 0.75% menthol dose (when they feel an urge to smoke), then they will go on to take one puff of the 1% dose (when they feel an urge to smoke). When subjects once again feel an urge to smoke, they will take up to ten puffs of the highest dose of the placebo formulation that they found tolerable and effective, and rate its effects. Then subjects will be randomised to take one puff of a range of 50mcg nicotine doses in random cross-over order. All these puffs will be taken on the same day, subjects will be asked to delay taking a puff of the next formulation until they once again feel an urge to smoke. The formulations that subjects will take in random order are: nicotine base, nicotine base plus menthol, nicotine base plus vanillin, nicotine lactate, nicotine lactate plus menthol, nicotine lactate plus vanillin. Subjects may then choose whether or not to take one puff of the 100mcg per puff dose of one or more of the formulations of which they sampled the 50mcg dose version (presented in the same random order as the 50mcg doses were). Subjects will only take a puff of the 100mcg dose of those formulations which they thought the 50mcg dose was tolerable. Subjects will take one puff of each of the 100mcg dose formulations, and after taking a puff of one formulation, they will wait until they feel an urge to smoke before they take a puff of the next formulation. Subjects can then choose to inhale one or more of the 200mcg doses of those formulations which they thought were tolerable at the lower doses. Just as they did with the lower dose formulations, before they take one puff of each of the 200mcg formulations, they will wait until they feel an urge to smoke before they take a puff of the next formulation, and they will only inhaler the higher dose of those formulations for which they felt the lower dose was tolerable. Subjects may then sample up to ten puffs of one or more of the formulations, which they thought was the most tolerable and efficacious. Subjects will be encouraged to choose the highest dose of the formulations that they thought were tolerable and efficacious (in terms of reducing the urge to smoke). The time over which subjects inhale the ten puffs will be limited to a maximum of ten minutes, and subjects can have a shorter duration if they wish. Subjects will wait until they feel an urge to smoke before they try the next formulation.
Intervention code [1] 269416 0
Treatment: Drugs
Comparator / control treatment
Cross-over of one placebo at three different doses; and different doses of different active formulations. The wash-out period between all treatments is the time that it takes for the subject to experience another urge to smoke. All these tests will be conducted on the same day. The purpose of having an ad libitum flexible wash-out period is that smokers differ a lot in their nicotine dependence, and the normal time gap between smoking their cigarettes. Therefore, by having a flexible wash-out period, subjects will have a similar urge to smoke before they try each formulation.
Control group
Placebo

Outcomes
Primary outcome [1] 279657 0
Tolerabiltiy (measured on a visual analogue scale)
Timepoint [1] 279657 0
Immediately after having one puff of each formulation, and then again, immediately after trying up to ten puffs of the formulation.
Secondary outcome [1] 294139 0
Score on the modified Cigarette Evaluation Scale
Timepoint [1] 294139 0
After inhaling up to ten puffs of one or more of the formulations. This will be scored within five minutes of completing the ten consecutive puffs.
Secondary outcome [2] 294140 0
Reduction in the brief-Questionnaire of Smoking Urges, after inhaling ten puffs of one or more of the formulations compared to the score prior to the inhalation.
Timepoint [2] 294140 0
Before and after inhaling ten puffs of the formulation. This will be recorded five minutes after the last puff of the ten consecutive puffs.
Secondary outcome [3] 294141 0
Side-effects of inhaling the formulations: hiccough, burned/hurt mouth, burned/hurt/scratched throat, interruption of smooth inspiratory flow, tasted bad, cough, excess salivation, hand tremble. All these will be assessed by self-report. The tremor will also be assessed by the researcher, by visual inspection of the hands when the subject's dominant arm and hand is stretched out straight in front of the subject
Timepoint [3] 294141 0
Five minutes after having the initial single puff of each formulation, and five minutes after having ten puffs of whichever formulation that subjects wish to have more of.
Secondary outcome [4] 294142 0
Order of preference of the formulations
Timepoint [4] 294142 0
After all the formulations have been inhaled (at least one puff)
Secondary outcome [5] 294143 0
The highest price and the score on a Juster Scale (the probablity that subjects would buy the inhaler at a range of different prices) for the price that subjects would pay for the inhaler formulations
Timepoint [5] 294143 0
After all the formulations have been inhaled (at least one puff)

Eligibility
Key inclusion criteria
Smoke more than 9 cigarettes per day. Have a brief-Fagerstrom Test of Nicotine Dependence score of 3 or more.
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
uncontrolled hypertension, uncontrolled diabetes, history of unstable angina or heart attack or stroke in the past 3 months, uncontrolled phaeochromocytoma, uncontrolled hyperthyroidism, psychiatric disorder severe enough to require ongoing care of a psychiatrist, pregnancy, breastfeeding, inadequate contraception, current use of any nicotine replacement therapy, taking medications that are metabolised by cytochrome CYP1A2 (imipramine, clozapine, opioid analgesics (e.g. propoxyphene), propranolol, verapamil, theophylline, insulin, pentazocline, tacrine, ropinirole, olanzapine, clomiprasmine, fluvoxamine)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The trial will be double-blind (subjects and research will be blind to what is in each inhaler, but they will not be blind to which is a 50mcg, a 100mcg, and a 200mcg dose; and the researcher will not be blind to the fact that the first three formulations are placebos. Masking of subjects and the researcher conducting the trial will be achieved by wrapping the canisters with a paper collar, which hides the label of the canister. The paper collars will be labelled A, B, C, D, E, F, G, and they will have the dosage strength as well (e.g. A50mcg, A100mcg, A200mcg). The first formulation (A) will always be the placebo. The order in which subjects will receive the six active formulations (B, C, D, E, F, or G) will be randomised by computer, and the assignments will be contained in tamper-proof sealed envelopes. A separate researcher who is not involved in the trial, will make the paper collars and put them on the canisters and will also make the randomisation list and place the assignments into the sealed tamper-proof envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The sequence will be generated by a computer.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
The purpose of this study is to pilot the acceptability and tolerability and efficay of a range of placebo and active nicotine formulations, to guide the design of a larger randomised placebo-controlled trial. All the inhaler tests will be conducted in a single visit. The reason that the order that the placebo is not randomised, is because we want to know whether people, who have had no prior experience of a nicotine inhaler, would think that the placebo might be active, or whether they would immediately know that it contained no nicotine. This is important because the placebo needs to be believable.
Phase
Phase 0
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 3850 0
New Zealand
State/province [1] 3850 0
North Island

Funding & Sponsors
Funding source category [1] 269888 0
Government body
Name [1] 269888 0
Health Research Council of New Zealand
Address [1] 269888 0
PO Box 5541, Wellesley Street, Auckland 1141.
Country [1] 269888 0
New Zealand
Primary sponsor type
Government body
Name
Health Research Council of New Zealand
Address
PO Box 5541, Wellesley Street, Auckland 1141.
Country
New Zealand
Secondary sponsor category [1] 268903 0
University
Name [1] 268903 0
University of Otago, Wellington
Address [1] 268903 0
PO Box 7343
Wellington South 6242
Country [1] 268903 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 271858 0
Central Region Ethics Committee
Ethics committee address [1] 271858 0
PO Box 5013
Wellington 6011
Ethics committee country [1] 271858 0
New Zealand
Date submitted for ethics approval [1] 271858 0
01/10/2010
Approval date [1] 271858 0
21/12/2010
Ethics approval number [1] 271858 0
CEN10/10/050

Summary
Brief summary
The aim of this small study, is to test the tolerability, efficacy, and side-effects of a series of placebo and nicotine inhaler formulations. We aim to test whether a menthol inhaler can act as a convincing placebo intervention. We aim to test whether pure nicotine (nicotine free base) is more or less tolerable to inhaler than nicotine lactate; and whether the addition of menthol, or vanillin improves the tolerability of these formulations.
Trial website
The trial website is not currently available, but it will be located at www.otago.ac.nz/wellington
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33179 0
Address 33179 0
Country 33179 0
Phone 33179 0
Fax 33179 0
Email 33179 0
Contact person for public queries
Name 16426 0
Brent Caldwell
Address 16426 0
University of Otago, Wellington
PO Box 7343
Wellington 6242
Country 16426 0
New Zealand
Phone 16426 0
+64 4 918 6041
Fax 16426 0
Email 16426 0
brent.caldwell@otago.ac.nz
Contact person for scientific queries
Name 7354 0
Brent Caldwell
Address 7354 0
University of Otago, Wellington
PO Box 7343
Wellington 6242
Country 7354 0
New Zealand
Phone 7354 0
+64 4 918 6041
Fax 7354 0
Email 7354 0
brent.caldwell@otago.ac.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary