Clinical trial NCT01438944: Evaluation of Transdermal Nicotine Replacement Therapy (NRT) Activity Through Metabolic Induction
Official title: Evaluation of Nicotine Receptor Up-regulation Activity Through Metabolic Induction and Changes in Responsiveness Using Surrogate Evaluation Methods
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Smoking
Addiction
Keywords: NRT
Patch
smoking
addiction
Lead sponsor: The Queen Elizabeth Hospital
Sponsor class: OTHER
Collaborators: name: Basil Hetzel Institute for Translational Research
name: University of Adelaide
name: University of South Australia
name: Clinical Practice Unit
name: Therapeutics Research Centre
First posted: 2011-09-22
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: Evaluation to determine if auto-induction can be used as a surrogate measure of nicotine receptor up-regulation through an observational study using nicotine replacement therapy for two weeks and no intervention for two weeks.

Detailed description: Studies have shown that prolonged exposure to nicotine reinforces addiction. The act of smoking delivers nicotine through lungs into the blood stream. As a result, during smoking nicotine levels peak and then when smoking stops levels progressively diminish to a base (trough) level. At the peak level a smoker feels rewarded, but at the trough level a smoker starts to experience negative withdrawal affects and a desire to smoke. Nicotine Gum and Inhalers mimic this smoking behaviour maintaining a peak and trough regime, but nicotine patches do not. Instead, nicotine patches deliver a constant base dose considered to be either above that of the smokers trough level or at a level where negative withdrawal effects are reduced.

The question arises as to if nicotine levels delivered by a patch are constant and potentially above that of the baseline smokers level, does this reinforce the addiction and therefore contribute to the high long term relapse rate? To answer this question the investigators will be looking at metabolites which the body uses to breakdown nicotine and several other enzymes. These metabolites respond to the levels of nicotine in the blood stream by increasing or decreasing over time. By testing blood flow, blood and urine the investigators are able to gain an insight into how the body is dealing with a constant stable dose of nicotine rather than a peak and trough dose. In combination with the questionnaires the investigators will be able to determine the level of affect.

Eligibility criteria: Inclusion Criteria:

* Smokers who currently smoke at least 10 cigarettes per day
* Aged between 18 and 75
* Informed consent
* Willingness to attempt to quit smoking for the period specified, initially with a transdermal patch for 14 days and then without any smoking cessation aids for a further 14 days.

Exclusion Criteria:

* Use of bupropion, champix or nicotine containing products other than cigarettes in the last 2 months
* previous reactions to NRT
* Pregnancy / Breast Feeding
* Uncontrolled hypertension
* Unstable angina
* Heart attack or stroke within the previous 6 months
* Severe Obesity as indicated by Body Mass Index (BMI) ≥35 (potential for slow release of nicotine from tissues)
* acute psychiatric illness, past history psychosis, suicidal ideation or current diminished capacity.
* Current treatment or recent diagnosis of cancer
* Current use of Phenobarbital or other anticonvulsant drugs (induction of metabolism of nicotine to cotinine)
* Renal failure (creatinine clearance\<30ml/min - reduces metabolic clearance of cotinine and nicotine)

Primary outcomes:
measure: Change from baseline Nicotine, cotinine, Leptin and orexin Metabolite ratios
timeFrame: Baseline, Day 4, Day 14 and Day 28
Secondary outcomes:
measure: Change from baseline Patient Instruments: Fagerstrom Test for Nicotine Dependence (FTND), Wisconsin Smoking Withdrawal Scale (WSWS), Michigan Nicotine Reinforcement Questionnaire (MNRQ), Smoker Diary
timeFrame: Baseline, Day 14 and Day 28
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Kristin Carson
state: South Australia
Study officials:
affiliation: University of Queeensland, University of South Australia
name: Michael Roberts, BPharm PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Queen Elizabeth Hospital, University of Adelaide
name: Brian Smith, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Therapeutics Research Centre
name: Thomas Robertson, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of South Australia
name: Micahel Ward, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Queen Elizabeth Hospital, University of Adelaide
name: John Beltrame, MBBS, FRACP
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Practice Unit
name: Malcolm Brinn, BHlthSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Practice Unit
name: Kritin Carson, PhD
role: PRINCIPAL_INVESTIGATOR
References: