Evaluation of Transdermal Nicotine Replacement Therapy (NRT) Activity Through Metabolic Induction

Evaluation of Nicotine Receptor Up-regulation Activity Through Metabolic Induction and Changes in Responsiveness Using Surrogate Evaluation Methods

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.

Study Overview

• Status: Completed
• Conditions: Smoking; Addiction
• Intervention / Treatment: Drug: Nicabate 21mg transdermal NRT

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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5044
      • Kristin Carson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Nicabate 21mg transdermal NRT; 21mg Transdermal NRT applied for 24hrs over a 14day period.	Drug: Nicabate 21mg transdermal NRT; Nicabate 21mg Transdermal NRT Patch applied daily for 14 days Testing at Baseline, Day 4, Day 14 and 14 days post.; Other Names: Nicotine replacement therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline Nicotine, cotinine, Leptin and orexin Metabolite ratios	Baseline Prior to Transdermal NRT patch application Day 4 NRT Patch Application Day 14 Last Day NRT Patch Application Day 28 14 Days post NRT patch removal.	Baseline, Day 4, Day 14 and Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline Patient Instruments: Fagerstrom Test for Nicotine Dependence (FTND), Wisconsin Smoking Withdrawal Scale (WSWS), Michigan Nicotine Reinforcement Questionnaire (MNRQ), Smoker Diary	Comparative evaluation patient instruments with ratios of metabolite induction	Baseline, Day 14 and Day 28

Collaborators and Investigators

• Sponsor: The Queen Elizabeth Hospital
• Collaborators: University of Adelaide; University of South Australia; Basil Hetzel Institute for Translational Research; Clinical Practice Unit; Therapeutics Research Centre
• Investigators: Principal Investigator: Michael Roberts, BPharm PhD, University of Queeensland, University of South Australia; Principal Investigator: Brian Smith, MBBS, PhD, Queen Elizabeth Hospital, University of Adelaide; Principal Investigator: Thomas Robertson, PhD, Therapeutics Research Centre; Principal Investigator: Micahel Ward, PhD, University of South Australia; Principal Investigator: John Beltrame, MBBS, FRACP, Queen Elizabeth Hospital, University of Adelaide; Principal Investigator: Malcolm Brinn, BHlthSc, Clinical Practice Unit; Principal Investigator: Kritin Carson, PhD, Clinical Practice Unit

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2011
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: September 20, 2011
• First Submitted That Met QC Criteria: September 21, 2011
• First Posted (Estimate): September 22, 2011

Study Record Updates

• Last Update Posted (Actual): April 10, 2017
• Last Update Submitted That Met QC Criteria: April 7, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: addiction; smoking; NRT; Patch
• Additional Relevant MeSH Terms: Compulsive Behavior; Impulsive Behavior; Behavior, Addictive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: 2011039

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Available upon request