Effects of IV Nicotine Induced Changes on BOLD fMRI Signal, Hormones, and Subjective Ratings of Stimulant Drug Effect

Nicotine Dependence Clinical Trial

Official title:

Effects of IV Nicotine Induced Changes on BOLD fMRI Signal, Hormones, and Subjective Ratings of Stimulant Drug Effect

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01588561
• Other study ID #: 2005-p-001656
• Secondary ID: R01DA025065
• Status: Completed
• Phase: N/A
• First received: April 6, 2012
• Last updated: October 26, 2015
• Start date: October 2005
• Est. completion date: September 2015

Study information

• Verified date: October 2015
• Source: Mclean Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Clinical studies are proposed to measure the covariance between nicotine-induced changes in endocrine, subjective and cardiovascular effects and the temporal concordance with increases in serum nicotine and cotinine levels. Possible gender and menstrual cycle phase influences on the effects of nicotine on hypothalamic-pituitary-adrenal axis (HPA) and hypothalamic-pituitary-gonadal axis (HPG) hormones have not been clearly delineated. Accordingly, the investigators propose to compare the acute effects of nicotine in men and women, and to study women at the follicular and the luteal phases of the menstrual cycle.

Description:

This clinical study will analyze the interactions between nicotine, endocrine hormone alterations, mood, cardiovascular measures, and patterns of brain activation to determine if they are affected by gender and menstrual cycle phase. These studies will advance our understanding of the neurobiology of nicotine's behavioral effects, and could be important in developing novel treatments for smoking cessation. Cigarette smoking remains a leading cause of death and disease and the proposed studies will advance knowledge of the ways in which gender and menstrual cycle phase may influence patterns of brain activation induced by nicotine and consequently the development and maintenance of nicotine dependence.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 145
• Est. completion date: September 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• 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.

• 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.

Exclusion Criteria:

• 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

• 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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator)

Related Conditions & MeSH terms

• Nicotine Dependence

Intervention

Drug:
• Intravenous Nicotine
Subjects will be given an IV challenge dose of nicotine or placebo in a constant volume of 2 mL on any study day. The nicotine solution (1.0 mg/70 kg or 1.5 mg/70 kg or 2.0mg/70 kg;) will be administered over 1 min. This rate of drug delivery (2 mL over one minute) has been safe in our IRB-approved studies of nicotine. Most investigators have administered IV nicotine over 10 seconds without any adverse reactions. The investigators concur with the IRB recommendation that the lower doses (1.0mg/70 kg and 1.5 mg/70 kg) should be administered first and the higher dose (2.0mg/70 kg ) will be administered last.

Locations

Country	Name	City	State
United States	Alcohol and Drug Abuse Research Center at McLean Hospital	Belmont	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Mclean Hospital	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effects of Nicotine on BOLD fMRI Signal	The investigators are examining the acute effects of IV nicotine on BOLD signal activation in areas of the brain with high levels of nicotine receptors.	From baseline to study completion (approximately 4 months for males and 8 months for females)	No
Primary	Effects of Nicotine on the hypothalamic-pituitary-gonadal (HPG) axis	The investigators are examining the effects of IV nicotine on serum nicotine levels and serum/plasma HPG hormone levels.	From baseline to study completion (approximately 4 months for males and 8 months for females)	No
Primary	Effects of Nicotine on hypothalamic-pituitary-adrenal axis (HPA) hormones	The investigators are examining the effects of IV nicotine on serum nicotine levels and serum/plasma hormone levels.	From baseline to study completion (approximately 4 months for males and 8 months for females)	No
Secondary	Effects of Nicotine on Mood States on the Visual Analog Scale	The investigators are examining the effects of IV nicotine on nicotine-induced changes in subjective states, as measured by a visual analog scale.	From baseline to study completion (approximately 4 months for males and 8 months for females)	No
Secondary	Effects of Nicotine on Cardiovascular Measures	The investigators are examining the effects of IV Nicotine induced changes and cardiovascular measures, as measured by blood pressure and heart rate.	From baseline to study completion (approximately 4 months for males and 8 months for females)	No