Trial Outcomes & Findings for Acetylcholine, Tobacco Smoking, Genes and Nicotinic Receptors (NCT NCT02008292)
NCT ID: NCT02008292
Last Updated: 2023-10-25
Results Overview
PET images will be obtained in healthy controls and smoker subjects after physostigmine administration. Change in ACh levels will be determined by change in binding potential of Norchloro-fluoro-homoepibatidine (NCFHEB)
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
80 participants
Primary outcome timeframe
first 150 minute scan at baseline, second 150 minute scan start 10 minutes post physostigmine administration
Results posted on
2023-10-25
Participant Flow
Healthy controls and healthy smokers will be recruited from the community through advertisements as approved by the Yale University Human Investigations Committee (HIC). Interested individuals contacting the clinic by phone in response to advertisements are told that the information they give over the phone is written down and discussed by the research team.
Participant milestones
| Measure |
Healthy Controls for 1210010989
men and women aged 18-60 years 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) that in the PI's determination puts the subject at increased risk or interferes with the study outcome. 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
|
Healthy Smoker Controls for 1210010989
men and women aged 18-60 years 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) that in the PI's determination puts the subject at increased risk or interferes with the study outcome. 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
|
|---|---|---|
|
Overall Study
STARTED
|
43
|
37
|
|
Overall Study
COMPLETED
|
43
|
37
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Acetylcholine, Tobacco Smoking, Genes and Nicotinic Receptors
Baseline characteristics by cohort
| Measure |
Healthy Controls for 1210010989
n=43 Participants
men and women aged 18-60 years 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) that in the PI's determination puts the subject at increased risk or interferes with the study outcome. 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
|
Healthy Smoker Controls for 1210010989
n=37 Participants
men and women aged 18-60 years 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) that in the PI's determination puts the subject at increased risk or interferes with the study outcome. 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
|
Total
n=80 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
43 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
80 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American
|
14 participants
n=5 Participants
|
13 participants
n=7 Participants
|
27 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
15 participants
n=5 Participants
|
17 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
10 participants
n=5 Participants
|
4 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
43 participants
n=5 Participants
|
37 participants
n=7 Participants
|
80 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: first 150 minute scan at baseline, second 150 minute scan start 10 minutes post physostigmine administrationPopulation: 66 of 80 participants were analyzed in primary study as 14 had signed consent but did not fully complete aim (i.e. Medical DQ by MD prior to drug administration or Relapse in smoking cessation by participant or medical aline failure, participant unable reschedule. For primary measure we only included participants that voluntarily completed both primary measures successfully.
PET images will be obtained in healthy controls and smoker subjects after physostigmine administration. Change in ACh levels will be determined by change in binding potential of Norchloro-fluoro-homoepibatidine (NCFHEB)
Outcome measures
| Measure |
ACH Levels in Healthy Controls After Physostigmine Administration
n=34 Participants
Physostigmine: Healthy Controls will receive physostigmine to induce elevated ACh levels in the brain.
|
ACH Levels in Smokers After Physostigmine Administration
n=32 Participants
Physostigmine: Smokers will receive physostigmine to induce elevated ACh levels in the brain.
|
|---|---|---|
|
Change in Acetylcholine (ACh) Levels After Physostigmine Administration as Confirmed by PET Images.
|
5.9 percentage of change
Standard Deviation 6.5
|
4.3 percentage of change
Standard Deviation 8.4
|
PRIMARY outcome
Timeframe: first 120 min scan at baseline, second 120 scan 2.5 hours after amphetamine administrationPopulation: 66 of 80 participants were analyzed in primary study as 14 had signed consent but did not fully complete aim (i.e. Medical DQ by MD prior to drug administration or Relapse in smoking cessation by participant or medical aline failure, participant unable reschedule. For primary measure we only included participants that voluntarily completed both primary measures successfully.
PET images will be obtained in all subjects after amphetamine administration. Change in DA levels will be determined by change in binding potential of PHNO, a selective dopamine D2 receptor agonist.
Outcome measures
| Measure |
ACH Levels in Healthy Controls After Physostigmine Administration
n=34 Participants
Physostigmine: Healthy Controls will receive physostigmine to induce elevated ACh levels in the brain.
|
ACH Levels in Smokers After Physostigmine Administration
n=32 Participants
Physostigmine: Smokers will receive physostigmine to induce elevated ACh levels in the brain.
|
|---|---|---|
|
Change in Dopamine (DA) Levels After Amphetamine Administration as Confirmed by PET Images.
|
26.5 percentage of change
Standard Deviation 6.5
|
19.6 percentage of change
Standard Deviation 10
|
Adverse Events
Healthy Controls for 1210010989
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Healthy Smoker Controls for 1210010989
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place