Nicotine DependenceNCT01588561

Nicotine Related Brain Activity: The Influence of Smoking History and Blood Nicotine Levels

A study testing Intravenous Nicotine in people with Nicotine Dependence, run by Mclean Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

In this study, we sought to explore brain activity in nicotine-dependent men in response to acute intravenous nicotine using pharmacological magnetic resonance imaging (phMRI). Read more about this study

Who is it for?: Ages 18 to 40 yearsHealthy volunteers can take part
Conditions the study is for: Nicotine Dependence
What is being tested?: Intravenous Nicotine
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 15 participants
Where: 1 siteUnited States
Study dates: Oct 2005to Sep 2015
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 40 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Men and women between the ages of 18 and 40 who currently smoke at least 15 cigarettes every day, and who fulfill DSM-IV diagnostic criteria for nicotine dependence will be eligible for participation.
No evidence of clinically significant disease based upon complete medical history and physical examination by a qualified physician.
Absence of DSM-IV Axis I Disorders other than nicotine dependence (305.10) as measured by the Structured Clinical Interview (SCID).
Routine laboratory blood tests including complete blood count, electrolytes, BUN and creatinine, liver function tests, hepatitis panel and urinalysis will be performed. Laboratory parameters must be within the normal range. HBsAg must be negative but subjects who have hepatitis serology consistent with previous exposure to Hepatitis A, Hepatitis B, or Hepatitis C, but who do not have clinical and biochemical evidence of acute infection, will be acceptable.
Hematocrit levels ≥ 39% for males and ≥ 35% for females.
Serum pregnancy test (hCG beta subunit) results must be negative within 24 hrs of the study day.

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Normal ECG.
A Body Mass Index (BMI-ratio of weight (W) to height (H) squared; W/H2=kg/m2) of between 18.0 and 27.0 for women and 21.4 to 29 for men.
Subjects must be able to read and understand instructions, as well as provide a valid informed consent.

Who cannot join

Participants with any lifetime DSM-IV Axis I disorder other than nicotine dependence.
Participants with clinically significant medical disorders.
Women who are pregnant as determined by laboratory testing for serum beta hCG.
Women who use hormonal contraceptive medications will not be accepted, because this would confound the hormonal measures.
Women with a mean BMI of outside the range 18.0-27.0 and men with a BMI outside the range 21.4-29.0.
Participants with ferromagnetic implants or other contraindications to fMRI

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Cardiac pacemakers
Metal clips on blood vessels (also called stents)
Artificial heart valves
Artificial arms, hands, legs, etc.
Brain stimulator devices
Implanted drug pumps
Ear implants
Eye implants or known metal fragments in eyes
Exposure to shrapnel or metal filings (wounded in military combat, sheet metal workers, welders, and others)
Other metallic surgical hardware in vital areas
Certain tattoos with metallic ink
Transdermal patches (eg. Orthro Evra, Nicoderm CQ)
Metal IUD (s)
Participants who describe themselves as seeking treatment will not be selected but will be referred to local smoking cessation programs.

Trial locations and contacts

1 site in 1 country.

United States1 site

Alcohol and Drug Abuse Research Center at McLean Hospital
Belmont, Massachusetts, 02478

Other trials in United States

About this study

Official title: Nicotine Related Brain Activity: The Influence of Smoking History and Blood Nicotine Levels, an Exploratory Study

In this study, we sought to explore brain activity in nicotine-dependent men in response to acute intravenous nicotine using pharmacological magnetic resonance imaging (phMRI).

Read the detailed description

phMRI was used to evaluate brain activity in response to 1.5 mg/70 kg intravenous nicotine or saline. The nicotine and saline were administered on different visits. The time courses of individual subjects' nicotine levels were used as regressors to assess neural activity relating to the infusions. The influence of Smoking history and physiological measures on the response to nicotine were also investigated.

Conditions: Nicotine Dependence
Being tested: Intravenous Nicotine, Saline - placebo
Medical subject headings: Tobacco Use Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Intravenous NicotineDrug
Also called IV Nicotine
Subjects received a single infusion of nicotine, 1.5 mg/70kg (New England Compounding Center, Framingham, MA), administered over 1 minute into the antecubital vein 10 minutes into their MRI scans.
Saline - placeboOther
Subjects received a single infusion of saline, administered over 1 minute into the antecubital vein 10 minutes into their MRI scans.

Study groups in NCT01588561
Study group	Role	What they receive
Intravenous Nicotine (1.5 mg/70 kg)	Active comparator	Participants are given a siingle infusion of nicotine (1.5 mg/70 kg), administered over 1 minute into the antecubital vein 10 minutes into their MRI scans Receives: Drug: Intravenous Nicotine
Saline - placebo	Placebo comparator	Participants are given physiological saline, administered over 1 minute into the antecubital vein 10 minutes into their MRI scans Receives: Other: Saline - placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Peak Nicotine Levels
Peak nicotine level in each participant
Measured: 0, 2, 4, 6, 8, 10, 12, 14, 16, 20, 30 minutes post-infusion
Number of Brain Regions With a Change in Brain Activity Relative to Saline
PhMRI analysis of the differential response of nicotine compared to the saline condition when analyzed with the nicotine time course.
The main dependent variable in this study, Blood Oxygen Level Dependent (BOLD) measures of brain activity (via fMRI) data does not exist in a vacuum-it is always relative to another measure of brain activity, typically collected at rest or after a placebo injection. So we collected the data after the IV placebo injection alone and the IV nicotine injection alone, but then need applied mathematical CONTRASTS to the data. This procedure results in the brain activity maps.
Measured: 40 minutes after infusion

Secondary outcomes (3)

Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With the Nicotine Time Course Controlling for Smoking History
PhMRI analysis of the differential response of nicotine compared to the saline condition when analyzed with the nicotine time course controlling for smoking history (pack years).
The main dependent variable in this study, Blood Oxygen Level Dependent (BOLD) measures of brain activity (via fMRI) data does not exist in a vacuum-it is always relative to another measure of brain activity, typically collected at rest or after a placebo injection. So we collected the data after the IV placebo injection alone and the IV nicotine injection alone, but then need applied mathematical CONTRASTS to the data. This procedure results in the brain activity maps.
Measured: 40 minutes after infusion
Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With Smoking History Controlling for Nicotine
PhMRI analysis of the differential response of nicotine compared to the saline condition when analyzed with smoking history (pack years) controlling for nicotine. The main dependent variable in this study, Blood Oxygen Level Dependent (BOLD) measures of brain activity (via fMRI) data does not exist in a vacuum-it is always relative to another measure of brain activity, typically collected at rest or after a placebo injection. So we collected the data after the IV placebo injection alone and the IV nicotine injection alone, but then need applied mathematical CONTRASTS to the data. This procedure results in the brain activity maps.
Measured: 40 minutes after infusion
Final Nicotine Levels
Final nicotine level in each participant
Measured: 30 minutes post-infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2005Sep 2015

First posted1 May 2012 (estimated)
Study startOct 2005
Primary completionJul 2015
Study completionSep 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Nicotine DependenceStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01588561
Sponsor's protocol ID: 2005-p-001656
Other IDs: R01DA025065
Status last verified: Jul 2017
First submitted: 6 Apr 2012
Last updated: 31 Aug 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Undecided

Publications

Yamamoto RT, Rohan ML, Goletiani N, Olson D, Peltier M, Renshaw PF, Mello NK. Nicotine related brain activity: the influence of smoking history and blood nicotine levels, an exploratory study. Drug Alcohol Depend. 2013 Apr 1;129(1-2):137-44. doi: 10.1016/j.drugalcdep.2012.10.002. Epub 2012 Oct 29.
PubMed 23117126

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Nicotine Dependence trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Nicotine Related Brain Activity: The Influence of Smoking History and Blood Nicotine Levels, an Exploratory Study
ClinicalTrials.gov ID: NCT01588561
Acronym / sponsor ID: 2005-p-001656
Conditions: Nicotine Dependence
Study type: Interventional
Recruitment status: Completed
Enrolment: 15 participants (actual)
Lead sponsor: Mclean HospitalUniversity, hospital or other
Collaborators: National Institute on Drug Abuse (NIDA)
Study start: Oct 2005
Primary completion: Jul 2015 (actual)
Study completion: Sep 2015 (actual)
First posted: 1 May 2012 (estimated)
Results: Posted 31 Aug 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

In this study, we sought to explore brain activity in nicotine-dependent men in response to acute intravenous nicotine using pharmacological magnetic resonance imaging (phMRI).

Detailed description

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Intravenous Nicotine (1.5 mg/70 kg)	Active comparator	Drug: Intravenous NicotineParticipants are given a siingle infusion of nicotine (1.5 mg/70 kg), administered over 1 minute into the antecubital vein 10 minutes into their MRI scans
Saline - placebo	Placebo comparator	Other: Saline - placeboParticipants are given physiological saline, administered over 1 minute into the antecubital vein 10 minutes into their MRI scans

Who may qualify

Ages: 18 to 40 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (9 listed)

Men and women between the ages of 18 and 40 who currently smoke at least 15 cigarettes every day, and who fulfill DSM-IV diagnostic criteria for nicotine dependence will be eligible for participation.
No evidence of clinically significant disease based upon complete medical history and physical examination by a qualified physician.
Absence of DSM-IV Axis I Disorders other than nicotine dependence (305.10) as measured by the Structured Clinical Interview (SCID).
Routine laboratory blood tests including complete blood count, electrolytes, BUN and creatinine, liver function tests, hepatitis panel and urinalysis will be performed. Laboratory parameters must be within the normal range. HBsAg must be negative but subjects who have hepatitis serology consistent with previous exposure to Hepatitis A, Hepatitis B, or Hepatitis C, but who do not have clinical and biochemical evidence of acute infection, will be acceptable.
Hematocrit levels ≥ 39% for males and ≥ 35% for females.

Key exclusion criteria (20 listed)

Participants with any lifetime DSM-IV Axis I disorder other than nicotine dependence.
Participants with clinically significant medical disorders.
Women who are pregnant as determined by laboratory testing for serum beta hCG.
Women who use hormonal contraceptive medications will not be accepted, because this would confound the hormonal measures.
Women with a mean BMI of outside the range 18.0-27.0 and men with a BMI outside the range 21.4-29.0.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Intravenous NicotineAlso: IV NicotineSubjects received a single infusion of nicotine, 1.5 mg/70kg (New England Compounding Center, Framingham, MA), administered over 1 minute into the antecubital vein 10 minutes into their MRI scans.	Drug	Intravenous Nicotine (1.5 mg/70 kg)
Saline - placeboSubjects received a single infusion of saline, administered over 1 minute into the antecubital vein 10 minutes into their MRI scans.	Other	Saline - placebo

Primary outcome

Peak Nicotine Levels
Time frame: 0, 2, 4, 6, 8, 10, 12, 14, 16, 20, 30 minutes post-infusion
Peak nicotine level in each participant
Number of Brain Regions With a Change in Brain Activity Relative to Saline
Time frame: 40 minutes after infusion
PhMRI analysis of the differential response of nicotine compared to the saline condition when analyzed with the nicotine time course. The main dependent variable in this study, Blood Oxygen Level Dependent (BOLD) measures of brain activity (via fMRI) data does not exist in a vacuum-it is always relative to another measure of brain activity, typically collected at rest or after a placebo injection. So we collected the data after the IV placebo injection alone and the IV nicotine injection alone, but then need applied mathematical CONTRASTS to the data. This procedure results in the brain activity maps.

3 secondary outcomes

Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With the Nicotine Time Course Controlling for Smoking History
Time frame: 40 minutes after infusion
Number of Brain Regions With a Change in Brain Activity Relative to Saline When Analyzed With Smoking History Controlling for Nicotine
Time frame: 40 minutes after infusion
Final Nicotine Levels
Time frame: 30 minutes post-infusion

Results and safety

Results posted to the registry on 31 Aug 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo First, Then Nicotine	14	14
Nicotine First, Then Placebo	1	1

Primary outcome: Peak Nicotine Levels

Time frame: 0, 2, 4, 6, 8, 10, 12, 14, 16, 20, 30 minutes post-infusion. Mean (Standard Deviation). Unit: ng/ml

Measure	Nicotine n = 14	Placebo n = 14
Value	16.1 (8)	0 (0)

Population analysed: Peak nicotine levels were only measured during the nicotine study intervention. One participant had incomplete serum nicotine results and was not included.

Primary outcome: Number of Brain Regions With a Change in Brain Activity Relative to Saline

Time frame: 40 minutes after infusion. Number. Unit: brain regions

Measure	Nicotine n = 12
Increased BOLD Signal	9
Decreased BOLD Signal	5

Population analysed: The data from three subjects were not included in the imaging results, one due to incomplete serum nicotine results, one due to a misalignment of the head in the scanner, which resulted in incomplete brain coverage, and one subject had a combination of excessive motion and abnormal anatomy.

3 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Nicotine	0 of 15 (0%)	2 of 15 (13.3%)	Not reported
Saline	0 of 15 (0%)	0 of 15 (0%)	Not reported

Limitations and caveats (from the sponsor): Small number of subjects completed due to a large shortage of Nicotine Bitartrate (the chemical used to create our IV Nicotine). We were unable to receive new nicotine shipments from 4/14 -2/15.Without this nicotine it was impossible to run subjects.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 23117126Yamamoto RT, Rohan ML, Goletiani N, Olson D, Peltier M, Renshaw PF, Mello NK. Nicotine related brain activity: the influence of smoking history and blood nicotine levels, an exploratory study. Drug Alcohol Depend. 2013 Apr 1;129(1-2):137-44. doi: 10.1016/j.drugalcdep.2012.10.002. Epub 2012 Oct 29.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Scott E. Lukas, PhD principal investigator

Mclean Hospital

Harrison G Pope, MD principal investigator

Mclean Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Intravenous Nicotine in people with Nicotine Dependence, run by Mclean Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Peak Nicotine Levels (time frame: 0, 2, 4, 6, 8, 10, 12, 14, 16, 20, 30 minutes post-infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01588561, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2017.