Ignite Creation Date:
2024-05-05 @ 5:27 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00463879
Status:
COMPLETED
Last Update Posted:
2007-12-12
First Post:
2007-04-18
Brief Title:
Galantamine for Cognitive Deficits in Schizophrenia
Sponsor:
Yale University
Organization:
Yale University
Study Overview
Official Title:
Galantamine for Cognitive Deficits in Schizophrenia
Status:
COMPLETED
Status Verified Date:
2007-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to determine the acute effects of the nicotinic receptor allosteric modulator galantamine 0 4 and 8 mg on neurocognitive function in schizophrenic smokers n20 versus schizophrenic nonsmokers n10 in an outpatient human laboratory setting
Detailed Description:
The proposed study will entail a comprehensive evaluation of the effects of acute doses of the nAChR allosteric modulator galantamine hydrochloride 0 4 and 8 mg on neurocognitive measures in schizophrenic smokers n20 and schizophrenic non-smokers n10 in a human laboratory paradigm After training on a battery of neurocognitive assessments all subjects will be studied during three separate test weeks where they will complete the neurocognitive batter at baseline and then again after acute administration of the three doses of galantamine in a counterbalanced order across subjects in each experimental group Specifically smokers would be randomized into one of two groups 1 those who undergo overnight smoking abstinence prior to the study cognitive sessions in order to determine galantamines effects on abstinence-induced cognitive impairment and 2 those who may smoke as usual prior to the study cognitive sessions The inclusion of nonsmokers will allow for the assessment of galantamines effects on cognitive deficits in schizophrenia independent of cigarette smoking Finally genetic variations in key metabolic genes involved in catecholamine metabolism COMT and DBH would be evaluated as determinants of galantamine-related improvements in cognitive performance in schizophrenic smokers and nonsmokers
We predict that galantamine will dose-dependently improve selected cognitive deficits associated with schizophrenia eg spatial working memory sustained attention and prepulse inhibition which we have previously shown are selectively improved by cigarette smoking in smokers with schizophrenia 18 and that this effect would be more pronounced in nonsmokers with schizophrenia If our results are positive they would support the rationale for controlled clinical trials using nAChR agonists like galantamine to treat selected domains of cognitive dysfunction in this disorder
Study Design
The following experimental groups will be studied
1 Schizophrenic Smokers under abstinence conditions n10
2 Schizophrenic Smokers in the smoking condition n10
3 Schizophrenic Nonsmokers n10
Three acute doses of galantamine GAL will be tested 0 4 and 8 mg in all subjects during three separate test sessions separated by at least 3 days with study medication doses across sequential subjects given in a randomized counterbalanced manner
Smokers n20 and nonsmokers n10 with schizophrenia will be recruited from the outpatient division of The Connecticut Mental Health Center CMHC in New Haven CT and its affiliated satellite centers Hispanic Clinic West Haven Mental Health Center and Yale Behavioral Mental Health Center
Screening Procedures
All potential subjects would meet with study staff over 2-3 intake and evaluation sessions to determine study eligibility which would typically take place within 4 weeks of study enrollment A description of the evaluation measures is given below
The screening evaluation will include completion of informed consent forms a urine toxicology screen to screen for recent use of illegal substances a urine pregnancy test for female subjects a psychiatric evaluation using the SCID for DSM-IV disorders PANSS AIMS Webster Barnes BDI Tiffany Questionnaire for Smoking Urges T-QSU Minnesota Nicotine Withdrawal Scale M-NWS Shipley Full Scale Intelligence Quotient IQ a blood draw for plasma nicotine plasma cotinine as well as CBC and LFTs and a physical examination conducted by Dr George Subjects will be separately consented for the genetics portion of the study and blood will be taken for genotyping purposes Finally a pre-study neuropsychological testing session would be performed in order to orient and train participants on the laboratory procedures Subjects who are pregnant or planning on becoming pregnant will not be eligible to participate
We will compensate all subjects who complete the screening and evaluation process 2500 and the neurocognitive training session 2500 for a total of 5000 In addition subjects would be paid 2500 for donating a blood sample for genotyping
Blood for genotyping will be obtained for COMT and DBH polymorphisms in smokers and nonsmokers in schizophrenia participating in this study The genotyping for these studies will be done in collaboration with the Psychiatric Genetics laboratory of Joseph F Cubells MD PhD at Emory University
Experimental Procedures Smokers will be tested on the cognitive battery at baseline Day 1 with periodic smoking breaks to minimize nicotine withdrawal and then again 24 hours later after overnight smoking abstinence Day 2 Non-smokers will be tested at baseline Day 1 and again 24 hours later Day 2 Study medications will be given as a single dose before the Day 2 session which will produce ascending plasma drug levels t ½ 57 h during the two hour testing session in a counterbalanced dosing schedule of galantamine hydrobromide 0 4 and 8 mg within each test group If systolic blood pressure is below 90 mm Hg the galantamine study medication will be held Before and after each session Day 1 and Day 2 clinical ratings using the PANSS HDRS extrapyramidal ratings and adverse event ratings would be completed For smokers pre-session tobacco craving and withdrawal ratings expired breath carbon monoxide and plasma cotinine and nicotine levels would be obtained Smokers randomized to the abstinence condition would receive 15000 for successful completion of each of the subsequent three test session procedures requiring overnight abstinence 5000 for successful abstinence and 10000 for subsequent testing session completion Smokers randomized to the non-abstinence condition would be also receiving 15000 for successful completion of each of the three test session procedures in order to maintain consistency Nonsmokers would receive 10000 for completion of each of the three test sessions beyond the training session In addition a completion bonus of 5000 will be paid to all subjects who complete all study procedures Thus smokers with schizophrenia could earn 57500 and nonsmokers 42500 for their completion of the entire study The proposed single subject timeline is given below
We predict that galantamine will dose-dependently improve selected cognitive deficits associated with schizophrenia eg spatial working memory sustained attention and prepulse inhibition which we have previously shown are selectively improved by cigarette smoking in smokers with schizophrenia 18 and that this effect would be more pronounced in nonsmokers with schizophrenia If our results are positive they would support the rationale for controlled clinical trials using nAChR agonists like galantamine to treat selected domains of cognitive dysfunction in this disorder
Study Design
The following experimental groups will be studied
1 Schizophrenic Smokers under abstinence conditions n10
2 Schizophrenic Smokers in the smoking condition n10
3 Schizophrenic Nonsmokers n10
Three acute doses of galantamine GAL will be tested 0 4 and 8 mg in all subjects during three separate test sessions separated by at least 3 days with study medication doses across sequential subjects given in a randomized counterbalanced manner
Smokers n20 and nonsmokers n10 with schizophrenia will be recruited from the outpatient division of The Connecticut Mental Health Center CMHC in New Haven CT and its affiliated satellite centers Hispanic Clinic West Haven Mental Health Center and Yale Behavioral Mental Health Center
Screening Procedures
All potential subjects would meet with study staff over 2-3 intake and evaluation sessions to determine study eligibility which would typically take place within 4 weeks of study enrollment A description of the evaluation measures is given below
The screening evaluation will include completion of informed consent forms a urine toxicology screen to screen for recent use of illegal substances a urine pregnancy test for female subjects a psychiatric evaluation using the SCID for DSM-IV disorders PANSS AIMS Webster Barnes BDI Tiffany Questionnaire for Smoking Urges T-QSU Minnesota Nicotine Withdrawal Scale M-NWS Shipley Full Scale Intelligence Quotient IQ a blood draw for plasma nicotine plasma cotinine as well as CBC and LFTs and a physical examination conducted by Dr George Subjects will be separately consented for the genetics portion of the study and blood will be taken for genotyping purposes Finally a pre-study neuropsychological testing session would be performed in order to orient and train participants on the laboratory procedures Subjects who are pregnant or planning on becoming pregnant will not be eligible to participate
We will compensate all subjects who complete the screening and evaluation process 2500 and the neurocognitive training session 2500 for a total of 5000 In addition subjects would be paid 2500 for donating a blood sample for genotyping
Blood for genotyping will be obtained for COMT and DBH polymorphisms in smokers and nonsmokers in schizophrenia participating in this study The genotyping for these studies will be done in collaboration with the Psychiatric Genetics laboratory of Joseph F Cubells MD PhD at Emory University
Experimental Procedures Smokers will be tested on the cognitive battery at baseline Day 1 with periodic smoking breaks to minimize nicotine withdrawal and then again 24 hours later after overnight smoking abstinence Day 2 Non-smokers will be tested at baseline Day 1 and again 24 hours later Day 2 Study medications will be given as a single dose before the Day 2 session which will produce ascending plasma drug levels t ½ 57 h during the two hour testing session in a counterbalanced dosing schedule of galantamine hydrobromide 0 4 and 8 mg within each test group If systolic blood pressure is below 90 mm Hg the galantamine study medication will be held Before and after each session Day 1 and Day 2 clinical ratings using the PANSS HDRS extrapyramidal ratings and adverse event ratings would be completed For smokers pre-session tobacco craving and withdrawal ratings expired breath carbon monoxide and plasma cotinine and nicotine levels would be obtained Smokers randomized to the abstinence condition would receive 15000 for successful completion of each of the subsequent three test session procedures requiring overnight abstinence 5000 for successful abstinence and 10000 for subsequent testing session completion Smokers randomized to the non-abstinence condition would be also receiving 15000 for successful completion of each of the three test session procedures in order to maintain consistency Nonsmokers would receive 10000 for completion of each of the three test sessions beyond the training session In addition a completion bonus of 5000 will be paid to all subjects who complete all study procedures Thus smokers with schizophrenia could earn 57500 and nonsmokers 42500 for their completion of the entire study The proposed single subject timeline is given below
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None