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Acetylcholine, Tobacco Smoking, Genes and Nicotinic Receptors (nic_physo)

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ClinicalTrials.gov Identifier: NCT02008292
Recruitment Status : Recruiting
First Posted : December 11, 2013
Last Update Posted : April 28, 2022
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Yale University

Brief Summary:

The purpose of the study is to measure the sensitivity of NCFHEB binding to changes in endogenous acetylcholine levels in healthy smoking and nonsmoking subjects, and in schizophrenic smoking and nonsmoking subjects. We hypothesize that physostigmine-induced elevated ACh levels will lead to a reduction in the availability of nicotinic receptors for the binding of the radioligand. We hypothesize there will be greater increase in ACh level (or greater reduction in radio tracer binding) in smoking as compared to nonsmoking subjects. We hypothesize there will be greater increase in ACh level (or greater reduction in radio tracer binding) in smoking as compared to nonsmoking subjects with schizophrenia, but the extent of this change will be different than in controls.

We are also measuring the sensitivity of PHNO binding to changes in dopamine levels in healthy smoking and nonsmoking subjects before and after amphetamine challenge.


Condition or disease Intervention/treatment Phase
Smoking Schizophrenia Drug: Physostigmine Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Acetylcholine, Tobacco Smoking, Genes and Nicotinic Receptors
Study Start Date : September 2013
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: physostigmine and amphetamine
There is only one arm to the study. All subjects will receive physostigmine and amphetamine.
Drug: Physostigmine
All subjects will receive physostigmine to induce elevated ACh levels in the brain.
Other Name: IV physostigmine




Primary Outcome Measures :
  1. Change in ACh levels at baseline and after physostigmine administration as confirmed by PET images. [ Time Frame: first 150 minute scan at baseline, second 150 minute scan start 10 minutes post physostigmine administration ]
    PET images will be obtained in healthy and schizophrenic subjects at baseline and after physostigmine administration. Change in ACh levels will be determined by change in binding potential of NCFHEB

  2. Change in DA levels at baseline and after amphetamine administration as confirmed by PET images. [ Time Frame: first 120 min scan at baseline, second 120 scan 2.5 hours after amphetamine administration ]
    PET images will be obtained in all subjects at baseline and after amphetamine administration. Change in DA levels will be determined by change in binding potential of PHNO.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • who are able to read and write
  • who are able to give voluntary written informed consent
  • have no current uncontrolled medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology
  • have no history of a neurological or psychiatric disorder (DSMIV Axis 1 and 2) other than schizophrenia in schizophrenia subgroup
  • have not regularly used any prescription, herbal or illegal psychotropic medications (e.g. antidepressants, antipsychotics, anxiolytics, ecstasy) in the past 6 months (controls).
  • Subjects with schizophrenia have not used any herbal or illegal substances in the past 6 months (medication inclusion listed below in Aim 5)
  • drink less than <21 drinks/week for women and less than <35 drinks per week for men
  • have not used marijuana in the past 30 days and have not met criteria for dependence in the past 2 years
  • If female, not pregnant or breast feeding
  • If female of childbearing age, must use an acceptable method of birth control, as determined by the principal investigator
  • do not suffer from claustrophobia or any MR contradictions
  • willing to donate blood for genetic studies
  • willing to be followed up monthly after study participation via phone or email contact

Exclusion Criteria:

  • Presence of acute or unstable medical or neurological illness. Subjects will be excluded from the study if they present with any history of serious medical or neurological illness or if they show signs of a major medical or neurological illness on examination or lab testing including history of seizures, head injury, brain tumor, heart, liver or kidney disease, eating disorder, diabetes.
  • Presence of an Axis I diagnosis other than nicotine dependence and schizophrenia (for schizophrenia subgroup) in the past 2 years
  • Regular use of any psychotropic drugs including anxiolytics and antidepressants and other over-the-counter medications and herbal products within the last year, and none within the last month for healthy controls.
  • Regular use of antidepressants or psychotropic over-the-counter medications and herbal products within the last year
  • For subjects with Schizophrenia, use of SSRI's (Paxil, Prozac Zoloft, Lexapro and Celexa) and use of tricyclic anti-depressants, except for a minimal dose used to treat anything other than depression, per the Investigator's discretion.
  • Pregnancy/Breast feeding
  • Subjects with a pacemaker or other ferromagnetic material in body.
  • Subjects with a sitting pulse rate >100 bpm will be excluded
  • Subjects with hypertension defined as sitting systolic blood pressure of >160 mmHg and/or sitting diastolic blood pressure of >100 mmHg will be excluded. Those individuals with hypertension that is well controlled by medication (e.g., within the above mentioned range) are not excluded
  • Specifically, we will exclude subjects who have any active clinically significant deviation from the normal range in their electrocardiogram (EKG). However, subjects who have abnormalities in their EKG but the condition has been present for a while and the study cardiologist has evaluated and feels comfortable with the condition, would not be excluded on the basis of their cardiac condition. Examples of conditions that may meet these criteria (e.g., condition has been present for a while) include but are not limited to T-wave abnormalities, atrial fibrillation, prolonged PR interval, and right bundle branch block.
  • Subjects with an allergy to salicylates
  • Subjects with history of prior radiation exposure for research purposes within the past year such that participation in this study would place them over FDA limits for annual radiation exposure. This guideline is an effective dose of 5 rem received per year.
  • Subjects with current, past or anticipated exposure to radiation in the work place
  • Blood donation within eight weeks of the start of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02008292


Contacts
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Contact: Kelly Cosgrove, PhD 203-737-6969 kelly.cosgrove@yale.edu
Contact: Jon Mikael Anderson, MSc 203-737-7074 jonmikael.anderson@yale.edu

Locations
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United States, Connecticut
Connecticut Mental Health Center Recruiting
New Haven, Connecticut, United States, 06519
Yale Magnetic Resonance Research Center Recruiting
New Haven, Connecticut, United States, 06519
Yale PET Center Recruiting
New Haven, Connecticut, United States, 06519
Sponsors and Collaborators
Yale University
National Institutes of Health (NIH)
National Institute on Drug Abuse (NIDA)
Investigators
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Principal Investigator: Kelly Cosgrove, PhD Yale University
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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02008292    
Other Study ID Numbers: 1210010989/2000021470
2R01DA015577-05 ( U.S. NIH Grant/Contract )
K23DA045957 ( U.S. NIH Grant/Contract )
R01DA038832 ( U.S. NIH Grant/Contract )
First Posted: December 11, 2013    Key Record Dates
Last Update Posted: April 28, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Yale University:
smoking
schizophrenia
acetylcholine
Additional relevant MeSH terms:
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Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Physostigmine
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Miotics
Autonomic Agents
Peripheral Nervous System Agents