SchizophreniaNCT01246128
Nicotinic Receptor Density in Smoking and Nonsmoking Schizophrenics
An observational study of Schizophrenia, run by National Institute on Drug Abuse (NIDA) at 2 sites in United States.
Trial summary
Background: Previous studies have suggested that smoking cigarettes affects the number of receptors in the brain for nicotine, a chemical present in cigarette smoke. The receptors play a role in an individual's ability to think and concentrate. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- 31 Oct 2010to 12 Jul 2011
- Phase
- Observational
- Are there results?
- None posted in the registry
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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age: Subjects will be male and female volunteers aged 18 to 50 years.
- Contact: All subjects must have a stable point of contact and must agree to participate in one PET study and one MRI scan.
- Smoking group: must smoke at least 10 cigarettes per day for at least the last year. They should have experience with abstaining from smoking for at least 48 h.
- Nonsmoking group: Subjects in the non-smoking group must be nonsmokers or have smoked less than 100 cigarettes in their lifetime and have ceased smoking at least two years before the start of the study.
- Diagnosis: Each volunteer will have a diagnosis of schizophrenia using DSMIV criteria. Each subject will have the following information available for diagnostic consideration: Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), a general psychiatric interview for past illness characteristics and family history, information from 2-3 months of independent clinician observation including current detailed mental status evaluations using the Brief Psychiatric Rating Scale (BPRS), Schedule for the Assessment of Positive and Negative Symptoms (SAPS/SANS), and Schedule for Deficit Syndrome (SDS). An assessment of impulsivity will also be done (Patton, 1995).
- Comorbidity: No subject with a current axis I diagnosis other than schizophrenia will be allowed. No subject with known claustrophobia will be allowed.
- Medications: Study participants will continue to take their antipsychotic medications that they have been taking for at least 3 months prior to the study. Haldol, risperidone and olanzapine will be allowed because of their lack of significant effect on the density of beta2 nACh receptors after prolonged administration to rats (Haldol; Breese et al., 2000; risperidone and olanzapine; personal communication, Mukhin, also SFN abstract).
Who cannot join
- Weight: Anyone weighing more than 300 lbs is excluded from the study. The purpose of this exclusion is the weight limit of the PET scanner.
- History of Drug Abuse: Participants reporting current or having a significant history of illicit drug abuse will be excluded from the study. Subjects may use moderate amounts of alcohol and caffeine and smoke an occasional marijuana cigarette, but must not be dependent on alcohol, caffeine or marijuana. No alcohol or marijuana for at least 72 hours prior to scanning. No smoking for 48 hrs before the PET scan.
- Current Medication Use: Participants will continue to use their prescription medications. The following hypertension medications will be exclusionary: Indapamide, spironolactone, clonidine, guanfacine, methyldopa, propranolol. Over the counter medications are not exclusionary, however, subjects will not be allowed to use over the counter medications in the week prior to their PET scan.
- CNS disease: History of known structural brain abnormalities (e.g., neoplasm, subarachnoid cysts), cerebrovascular disease, infectious disease (e.g., abscess), history of head trauma (defined as documented loss of consciousness for 5 min or greater), history of seizures as an adult, sleep apnea.
- Cardiovascular, pulmonary, or systemic disease: Untreated hypertension known arrhythmia, symptomatic or known coronary artery disease; history of endocarditis, cerebral embolism, obstructive pulmonary disease, asthma, active tuberculosis, known endocrine disease (derangements in adrenal, thyroid, bone or reproductive function) known chronic renal or hepatic dysfunction, known HIV seropositive, known current autoimmune disease involving the CNS, type I diabetes mellitus. Subjects with type II diabetes mellitus will be allowed if their Hb A1C is less than 7.
- Special considerations for female subjects. Female participants who are planning to become pregnant, currently pregnant or nursing will not be allowed to participate in this study because of potential damage to the fetus or baby from the radiation. In addition, women of child bearing age who are sexually active are required to use an effective form of birth control for the duration of the study. Effective forms of birth control include:
Show all 15Show fewer
- hormonal contraceptives (birth control pills, injectable hormones, vaginal ring hormones),
- surgical sterility (tubal ligation or hysterectomy)
- IUD
- Diaphragm with spermicide
- Condom with spermicide
- Female subjects will be given a serum pregnancy test (quantitative beta HCG) within 24 hours of the PET study. Menstrual cycle phase or sex has not been shown to affect receptor availability (Cosgrove et al., 2007).
- Radiation exposure: Any subject who has participated in any research studies in which he/she received a radiation exposure that would result in combination with the present study, in a total effective radiation exposure (from research studies) exceeding 5.0 rem in a year.
- Children under the age of 18 will be excluded to avoid unnecessary exposure to radiation to these populations.
- Presence in body of metallic implants or materials that could be moved by the magnet of the MRI scanner: pacemakers, surgical implants, aneurysm clips, dental braces, bullet(s) or other metallic materials.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Johns Hopkins University
Baltimore, Maryland, 21205
Maryland Psychiatric Research Center (MPRC) 55 Wade Avenue
Catonsville, Maryland, 21228
About this study
Official title: PET Assay of Acetylcholine Beta2* Nicotinic Receptor Density in Smoking and Non-Smoking Schizophrenics
Background:
- Previous studies have suggested that smoking cigarettes affects the number of receptors in the brain for nicotine, a chemical present in cigarette smoke. The receptors play a role in an individual's ability to think and concentrate. Many people with schizophrenia and similar disorders smoke, and research suggests that smoking may temporarily improve concentration and focus in individuals with schizophrenia. Researchers are interested in studying both current smokers and nonsmokers with schizophrenia to determine whether smoking affects the number of nicotine receptors in the brains of people with schizophrenia.
Read more
Objectives:
- To study the distribution and volume of nicotine receptors in the brains of individuals with schizophrenia who are either nonsmokers or current smokers.
Eligibility:
- Individuals between 18 and 50 years of age who have been diagnosed with schizophrenia and are either nonsmokers or current smokers (at least 10 cigarettes per day for the past year).
- Current smokers must be able to give up smoking for 48 hours.
Design:
- This study involves an initial screening visit and up to five study visits.
- After the screening visit, participants will have two sessions in which they will complete questionnaires about thoughts, memory, and smoking habits. Smokers will also have nicotine blood and carbon monoxide breath levels taken during these sessions, before and after smoking a cigarette.
- Participants will have sessions with imaging studies (e.g., magnetic resonance imaging) to provide baseline measurements for later tests, and will also have tests to measure brain electrical activity.
- Participants will have a positron emission tomography (PET) scanning session to examine the nicotine receptors in the brain. Participants will need to stay overnight (nonsmokers) or for 2 nights (smokers) as an inpatient before the session. The PET scan session will take up to 6 hours, although participants will only be in the scanner for up to 3 hours.
- Participants will have a follow-up phone call with study researchers 1 week after the PET scanning session.
Read the detailed description
Objective:
The objective of this study is to determine the distribution and volume of distribution (Vt) in vivo of Beta2* acetylcholine receptors (Beta2* nAChR) in schizophrenic smokers and nonsmokers and compare this to published data from normal healthy subjects who are smokers and nonsmokers.
Study population:
Participants will be volunteers with a diagnosis of schizophrenia aged 18 to 50 years. The proposed sample size is 10 per group: nonsmokers or ex-smokers and smokers for a total of 20 participants.
Design:
One PET study lasting up to 8 hours after combination of bolus and continuous infusion administration of 2[(18)F] FA-85380. Smokers will be abstinent for at least 48 hrs. Subjects will also undergo a structural MRI scan for purposes of registration of PET scan data.
Outcome Measures:
Data from 20 schizophrenic patients (10 smokers and 10 nonsmokers) will be compared to published data from healthy controls. Total volume of distribution (VT) which is a measure of receptor density and distribution of Beta2 nAChR* will be determined in Schizophrenic smokers and nonsmokers and differences in these values will be compared to published values for the differences in nicotinic acetylcholine receptor density in healthy smokers and nonsmokers (Mukhin et al., 2008) Also, receptor distribution and VT will be correlated with levels of smoking and symptom profiles in the schizophrenic patients studied.
- Conditions
- Schizophrenia
- Keywords
- Nicotinic Acetylcholine Receptors, Schizophrenia Smokers, PET Imaging
- Medical subject headings
- Schizophrenia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2010 (estimated)
- Study start31 Oct 2010
- Study completion12 Jul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies 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
- Observational
- Time perspective
- Other
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Drug Abuse (NIDA)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01246128
- Sponsor's protocol ID
- 999911463
- Other IDs
- 11-DA-N463
- Status last verified
- 12 Jul 2011
- First submitted
- 20 Nov 2010
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Adler LE, Hoffer LJ, Griffith J, Waldo MC, Freedman R. Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics. Biol Psychiatry. 1992 Oct 1;32(7):607-16. doi: 10.1016/0006-3223(92)90073-9.
PubMed 1450287Adler LE, Hoffer LD, Wiser A, Freedman R. Normalization of auditory physiology by cigarette smoking in schizophrenic patients. Am J Psychiatry. 1993 Dec;150(12):1856-61. doi: 10.1176/ajp.150.12.1856.
PubMed 8238642Bottlaender M, Valette H, Roumenov D, Dolle F, Coulon C, Ottaviani M, Hinnen F, Ricard M. Biodistribution and radiation dosimetry of 18F-fluoro-A-85380 in healthy volunteers. J Nucl Med. 2003 Apr;44(4):596-601.
PubMed 12679405
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PET Assay of Acetylcholine Beta2* Nicotinic Receptor Density in Smoking and Non-Smoking Schizophrenics
- ClinicalTrials.gov ID
- NCT01246128
- Acronym / sponsor ID
- 999911463
- Conditions
- Schizophrenia
- Keywords
- Nicotinic Acetylcholine Receptors, Schizophrenia Smokers, PET Imaging
- Study type
- Observational
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute on Drug Abuse (NIDA)US National Institutes of Health
- Study start
- 31 Oct 2010
- Study completion
- 12 Jul 2011
- First posted
- 23 Nov 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Previous studies have suggested that smoking cigarettes affects the number of receptors in the brain for nicotine, a chemical present in cigarette smoke. The receptors play a role in an individual's ability to think and concentrate. Many people with schizophrenia and similar disorders smoke, and research suggests that smoking may temporarily improve concentration and focus in individuals with schizophrenia. Researchers are interested in studying both current smokers and nonsmokers with schizophrenia to determine whether smoking affects the number of nicotine receptors in the brains of people with schizophrenia.
Objectives:
- To study the distribution and volume of nicotine receptors in the brains of individuals with schizophrenia who are either nonsmokers or current smokers.
Eligibility:
- Individuals between 18 and 50 years of age who have been diagnosed with schizophrenia and are either nonsmokers or current smokers (at least 10 cigarettes per day for the past year).
- Current smokers must be able to give up smoking for 48 hours.
Design:
- This study involves an initial screening visit and up to five study visits.
- After the screening visit, participants will have two sessions in which they will complete questionnaires about thoughts, memory, and smoking habits. Smokers will also have nicotine blood and carbon monoxide breath levels taken during these sessions, before and after smoking a cigarette.
- Participants will have sessions with imaging studies (e.g., magnetic resonance imaging) to provide baseline measurements for later tests, and will also have tests to measure brain electrical activity.
- Participants will have a positron emission tomography (PET) scanning session to examine the nicotine receptors in the brain. Participants will need to stay overnight (nonsmokers) or for 2 nights (smokers) as an inpatient before the session. The PET scan session will take up to 6 hours, although participants will only be in the scanner for up to 3 hours.
- Participants will have a follow-up phone call with study researchers 1 week after the PET scanning session.
Detailed description
Objective:
The objective of this study is to determine the distribution and volume of distribution (Vt) in vivo of Beta2* acetylcholine receptors (Beta2* nAChR) in schizophrenic smokers and nonsmokers and compare this to published data from normal healthy subjects who are smokers and nonsmokers.
Study population:
Participants will be volunteers with a diagnosis of schizophrenia aged 18 to 50 years. The proposed sample size is 10 per group: nonsmokers or ex-smokers and smokers for a total of 20 participants.
Design:
One PET study lasting up to 8 hours after combination of bolus and continuous infusion administration of 2[(18)F] FA-85380. Smokers will be abstinent for at least 48 hrs. Subjects will also undergo a structural MRI scan for purposes of registration of PET scan data.
Outcome Measures:
Data from 20 schizophrenic patients (10 smokers and 10 nonsmokers) will be compared to published data from healthy controls. Total volume of distribution (VT) which is a measure of receptor density and distribution of Beta2 nAChR* will be determined in Schizophrenic smokers and nonsmokers and differences in these values will be compared to published values for the differences in nicotinic acetylcholine receptor density in healthy smokers and nonsmokers (Mukhin et al., 2008) Also, receptor distribution and VT will be correlated with levels of smoking and symptom profiles in the schizophrenic patients studied.
Study design
- Time perspective
- Other
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Age: Subjects will be male and female volunteers aged 18 to 50 years.
- Contact: All subjects must have a stable point of contact and must agree to participate in one PET study and one MRI scan.
- Smoking group: must smoke at least 10 cigarettes per day for at least the last year. They should have experience with abstaining from smoking for at least 48 h.
- Nonsmoking group: Subjects in the non-smoking group must be nonsmokers or have smoked less than 100 cigarettes in their lifetime and have ceased smoking at least two years before the start of the study.
- Diagnosis: Each volunteer will have a diagnosis of schizophrenia using DSMIV criteria. Each subject will have the following information available for diagnostic consideration: Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), a general psychiatric interview for past illness characteristics and family history, information from 2-3 months of independent clinician observation including current detailed mental status evaluations using the Brief Psychiatric Rating Scale (BPRS), Schedule for the Assessment of Positive and Negative Symptoms (SAPS/SANS), and Schedule for Deficit Syndrome (SDS). An assessment of impulsivity will also be done (Patton, 1995).
Key exclusion criteria (15 listed)
- Weight: Anyone weighing more than 300 lbs is excluded from the study. The purpose of this exclusion is the weight limit of the PET scanner.
- History of Drug Abuse: Participants reporting current or having a significant history of illicit drug abuse will be excluded from the study. Subjects may use moderate amounts of alcohol and caffeine and smoke an occasional marijuana cigarette, but must not be dependent on alcohol, caffeine or marijuana. No alcohol or marijuana for at least 72 hours prior to scanning. No smoking for 48 hrs before the PET scan.
- Current Medication Use: Participants will continue to use their prescription medications. The following hypertension medications will be exclusionary: Indapamide, spironolactone, clonidine, guanfacine, methyldopa, propranolol. Over the counter medications are not exclusionary, however, subjects will not be allowed to use over the counter medications in the week prior to their PET scan.
- CNS disease: History of known structural brain abnormalities (e.g., neoplasm, subarachnoid cysts), cerebrovascular disease, infectious disease (e.g., abscess), history of head trauma (defined as documented loss of consciousness for 5 min or greater), history of seizures as an adult, sleep apnea.
- Cardiovascular, pulmonary, or systemic disease: Untreated hypertension known arrhythmia, symptomatic or known coronary artery disease; history of endocarditis, cerebral embolism, obstructive pulmonary disease, asthma, active tuberculosis, known endocrine disease (derangements in adrenal, thyroid, bone or reproductive function) known chronic renal or hepatic dysfunction, known HIV seropositive, known current autoimmune disease involving the CNS, type I diabetes mellitus. Subjects with type II diabetes mellitus will be allowed if their Hb A1C is less than 7.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 1450287Adler LE, Hoffer LJ, Griffith J, Waldo MC, Freedman R. Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics. Biol Psychiatry. 1992 Oct 1;32(7):607-16. doi: 10.1016/0006-3223(92)90073-9.
- Background: PubMed 8238642Adler LE, Hoffer LD, Wiser A, Freedman R. Normalization of auditory physiology by cigarette smoking in schizophrenic patients. Am J Psychiatry. 1993 Dec;150(12):1856-61. doi: 10.1176/ajp.150.12.1856.
- Background: PubMed 12679405Bottlaender M, Valette H, Roumenov D, Dolle F, Coulon C, Ottaviani M, Hinnen F, Ricard M. Biodistribution and radiation dosimetry of 18F-fluoro-A-85380 in healthy volunteers. J Nucl Med. 2003 Apr;44(4):596-601.
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Schizophrenia, run by National Institute on Drug Abuse (NIDA) at 2 sites 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 7 inclusion and 15 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: withdrawn, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. 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?
The study was withdrawn before enrolling participants, so there are no results.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01246128, which also lists 3 linked publications.
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 2 Jul 2017.