Nicotine Dependence, Tobacco Dependence
Conditions
Keywords
tobacco dependence, tobacco treatment, omega 3 series, polyunsaturated fatty acids
Brief summary
Nicotine dependence may prolong the exposure to toxic substances that cause various diseases. The Central Nervous System (CNS) is consisted by a large amount of Polyunsaturated Fatty Acids (PUFAS) from omega-3 serie. Omega-3 takes part in several actions, including the modulation of dopaminergic neurotransmission. In its deficiency is detected a hypofunctioning of the mesolimbic and mesocortical pathway, related to the reward system, involved on the context of nicotine dependence. Treatment using dietary supplementation with omega-3 shows improvements in several diseases, including mood disorders such as anxiety and depression. The investigators hypothesis is that supplementation with these fatty acids can restore the levels of omega-3 and could decrease nicotine dependence. The investigators objective is to investigate a possible association between increased serum levels of omega-3 and the reduction in nicotine dependence.
Detailed description
Introduction: A cigarette has more than 6,000 toxic substances that can cause various diseases. Nicotine dependence may prolong the exposure to these toxic substances. The Central Nervous System (CNS) is consisted by a large amount of Polyunsaturated Fatty Acids (PUFAS) from omega-3 serie. Omega-3 takes part in several actions, including the modulation of dopaminergic neurotransmission. In its deficiency is detected a hypofunctioning of the mesolimbic and mesocortical pathway, related to the reward system, involved on the context of nicotine dependence. Treatment using dietary supplementation with omega-3 shows improvements in several diseases, including mood disorders such as anxiety and depression. The investigators hypothesis is that supplementation with these fatty acids can restore the levels of omega-3 and could decrease nicotine dependence. Objective: Investigate a possible association between increased serum levels of omega-3 and the reduction in nicotine dependence. Material and Methods: In the clinical study, placebo controlled, double-blind, parallel, randomized, will be administered to 60 volunteers: placebo or fish oil for 90 days. Psychometric assessments will be carried out, measurements of serum levels of PUFAS, levels of carbon monoxide (CO) and cotinine in plasma will be done for monitoring the clinical course. Data Analysis: Repeated measures (ANOVA) for the dependent variables (dependency, anxiety, depression, motivation, compulsion, dosage of PUFAS, exhaled CO and cotinine) and independent (groups and time) to check for significant differences. If so, a second ANOVA with covariates will be conducted. Significance is p \<0.05 in all analyzes.
Interventions
DRUGPlacebo
mineral oil + food dye #2 (simulating the colour of essential fatty acids); 1000 mg of mineral oil per capsule
DRUGOmega 3
Each fish oil capsule contained 210.99 mg of EPA and 129.84 mg of DHA.
Sponsors
Federal University of São Paulo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy smokers; age between 20 and 60 years; score in Fagerström Test for Nicotine Dependence (FTND) up to 5 points (FTND \> 5); high motivation to stop smoking (accessed by Richmond Test)
Exclusion criteria
* psychiatric disorders; taking psychoactive medications; history of alcohol and/or other drugs abuse or dependence;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fageström Test for Nicotine Dependence Score at Baseline and After 90 Days of the Treatment | Baseline (prior to the beginning) and after 90 days of the treatment | The Fageström Test for Nicotine Dependence is a widely used test to measure the nicotine dependence. This test was chosen to evaluate the possible changes on the nicotine dependence during the clinical trial. The range for the scale is: very low (dependence) 0-2 low (dependence) 3-4 moderate (dependence) 5 high (dependence) 6-7 very high (dependence) 8-10 So, lower levels (low scores on the scale) of the FTND measure indicates lower nicotine dependence, and higher levels (high scores on the scales) of the FTND measure indicates higher nicotine dependence. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Docosahexaenoic Acid (DHA) at Baseline and After 90 Days of Treatment | At baseline (prior to the beginning of the treatment) and after 90 days of treatment | The polyunsaturated fatty acid Docosahexaenoic acid (DHA) is one of the main fatty acids omega-3 series. The dosage of these analyte was achieved by means of Liquid Chromatography - Mass Spectrometry Mass Spectrometry - LS-MS-MS. |
| Concentration of Eicosapentaenoic Acid (EPA) | At baseline (prior to the beginning of the treatment) and after 90 days of treatment | The polyunsaturated fatty acid Eicosapentaenoic acid (EPA) is one of the main fatty acids omega-3 series. The dosage of these analyte was achieved by means of Liquid Chromatography - Mass Spectrometry Mass Spectrometry - LS-MS-MS. |
Countries
Brazil
Participant flow
Recruitment details
Data were collected in São Paulo/Brazil between January 2013 and August 2013. All participants signed an informed consent prior to the beginning of the study. The participants did not receive any kind of compensation for participation in the study.
Pre-assignment details
No participants were excluded.
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo capsules 1,000 mg - mineral oil + food dye #2 (simulating the colour of essential fatty acids), taken in 3 daily doses, for 90 days. | 29 |
| Omega3 omega 3 capsules 1,000 mg fish oil taken as 3 daily doses, for 90 days. Each fish oil capsule contained 210.99 mg of EPA and 129.84 mg of DHA | 29 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 11 | 8 |
Baseline characteristics
| Characteristic | Placebo | Omega3 | Total |
|---|---|---|---|
| Age, Continuous | 47.8 years STANDARD_DEVIATION 11.5 | 46.2 years STANDARD_DEVIATION 11.1 | 47 years STANDARD_DEVIATION 11.3 |
| Body Mass Index (BMI) | 24.3 kg/m^2 STANDARD_DEVIATION 4.7 | 24.7 kg/m^2 STANDARD_DEVIATION 3.9 | 24.5 kg/m^2 STANDARD_DEVIATION 4.3 |
| Sex: Female, Male Female | 15 Participants | 13 Participants | 28 Participants |
| Sex: Female, Male Male | 14 Participants | 16 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 29 |
| other Total, other adverse events | 0 / 29 | 0 / 29 |
| serious Total, serious adverse events | 0 / 29 | 0 / 29 |
Outcome results
Primary
Fageström Test for Nicotine Dependence Score at Baseline and After 90 Days of the Treatment
The Fageström Test for Nicotine Dependence is a widely used test to measure the nicotine dependence. This test was chosen to evaluate the possible changes on the nicotine dependence during the clinical trial. The range for the scale is: very low (dependence) 0-2 low (dependence) 3-4 moderate (dependence) 5 high (dependence) 6-7 very high (dependence) 8-10 So, lower levels (low scores on the scale) of the FTND measure indicates lower nicotine dependence, and higher levels (high scores on the scales) of the FTND measure indicates higher nicotine dependence.
Time frame: Baseline (prior to the beginning) and after 90 days of the treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Fageström Test for Nicotine Dependence Score at Baseline and After 90 Days of the Treatment | pre | 6.53 units on a scale | Standard Deviation 2.01 |
| Placebo | Fageström Test for Nicotine Dependence Score at Baseline and After 90 Days of the Treatment | post | 5.96 units on a scale | Standard Deviation 1.85 |
| Omega3 | Fageström Test for Nicotine Dependence Score at Baseline and After 90 Days of the Treatment | pre | 6.56 units on a scale | Standard Deviation 1.52 |
| Omega3 | Fageström Test for Nicotine Dependence Score at Baseline and After 90 Days of the Treatment | post | 5.22 units on a scale | Standard Deviation 2.15 |
Secondary
Concentration of Docosahexaenoic Acid (DHA) at Baseline and After 90 Days of Treatment
The polyunsaturated fatty acid Docosahexaenoic acid (DHA) is one of the main fatty acids omega-3 series. The dosage of these analyte was achieved by means of Liquid Chromatography - Mass Spectrometry Mass Spectrometry - LS-MS-MS.
Time frame: At baseline (prior to the beginning of the treatment) and after 90 days of treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Concentration of Docosahexaenoic Acid (DHA) at Baseline and After 90 Days of Treatment | Pre | 747.71 ng/ml | Standard Deviation 794 |
| Placebo | Concentration of Docosahexaenoic Acid (DHA) at Baseline and After 90 Days of Treatment | Post | 663.93 ng/ml | Standard Deviation 767.41 |
| Omega3 | Concentration of Docosahexaenoic Acid (DHA) at Baseline and After 90 Days of Treatment | Pre | 645.38 ng/ml | Standard Deviation 757.49 |
| Omega3 | Concentration of Docosahexaenoic Acid (DHA) at Baseline and After 90 Days of Treatment | Post | 1,004.94 ng/ml | — |
Secondary
Concentration of Eicosapentaenoic Acid (EPA)
The polyunsaturated fatty acid Eicosapentaenoic acid (EPA) is one of the main fatty acids omega-3 series. The dosage of these analyte was achieved by means of Liquid Chromatography - Mass Spectrometry Mass Spectrometry - LS-MS-MS.
Time frame: At baseline (prior to the beginning of the treatment) and after 90 days of treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Concentration of Eicosapentaenoic Acid (EPA) | Pre | 77.00 ng/ml | Standard Deviation 67.72 |
| Placebo | Concentration of Eicosapentaenoic Acid (EPA) | Post | 77.39 ng/ml | Standard Deviation 73.22 |
| Omega3 | Concentration of Eicosapentaenoic Acid (EPA) | Pre | 86.76 ng/ml | Standard Deviation 111.79 |
| Omega3 | Concentration of Eicosapentaenoic Acid (EPA) | Post | 174.87 ng/ml | Standard Deviation 285.37 |
Post Hoc
Concentration of Serum Cotinine at Baseline and After 90 Days of Treatment
Cotinine is the major metabolite of nicotine, making it its primary metabolite. Cotinine dosage is considered one of the best parameters to distinguish smokers from non-smokers as well as for the nicotine graduation consumption. The traditional cut off value used to distinguish between smokers and non-smokers is 15 ng/mL for dosages from plasma sample
Time frame: At baseline (prior to the beginning of the treatment) and after 90 days of treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Concentration of Serum Cotinine at Baseline and After 90 Days of Treatment | Pre | 101.20 ng/ml | Standard Deviation 65.1 |
| Placebo | Concentration of Serum Cotinine at Baseline and After 90 Days of Treatment | Post | 97.79 ng/ml | Standard Deviation 63.26 |
| Omega3 | Concentration of Serum Cotinine at Baseline and After 90 Days of Treatment | Pre | 129.38 ng/ml | Standard Deviation 85.15 |
| Omega3 | Concentration of Serum Cotinine at Baseline and After 90 Days of Treatment | Post | 98.54 ng/ml | Standard Deviation 61.94 |
p-value: <0.05ANOVA
p-value: <0.01ANOVA
p-value: <0.01t-test, 1 sided
p-value: <0.01t-test, 1 sided