what would antipsychotics do to a normal person
Brief Summary:
The primary aim of this written report is to investigate antipsychotic drug furnishings on healthy brain metabolism.
| Condition or illness | Intervention/treatment | Stage |
|---|---|---|
| Healthy | Drug: Olanzapine | Phase 4 |
Detailed Clarification:
Schizophrenia is a circuitous psychiatric disorder characterized past alterations in brain construction. It is not clear yet whether some of these alterations are primarily related to pathophysiology of illness per se or consequence of brain exposure to the effects of psychotropic drugs. In contempo years accumulating evidence suggests that exposure to the effects of psychotropic drugs may contribute to the structural and other changes in encephalon. Therefore, apply of antipsychotic medications equally treatment for schizophrenia represents a potential misreckoning factor in many of the studies. Well-nigh neuroimaging studies of schizophrenia to date have not included the examination of not-medicated patients, making conclusions about medication effects on neuroimaging measures difficult. MRI studies of structural encephalon changes across fourth dimension are limited by the fact that due to ethical reasons neither untreated subjects with schizophrenia nor command subjects exposed to antipsychotic medications tin can be used as comparing groups. There are some preclinical rat and primate models which revealed chronic antipsychotic-induced alterations in the brain. However few studies investigate the furnishings of chronic exposure to antipsychotic drugs on healthy human brain. Therefore in this written report, investigators aimed to evaluate brain alterations induced past chronic drug exposure in healthy volunteers. To address this problem, nosotros will comport a single-site, single arm, open up-label, interventional, multimodal neuroimaging report of healthy comparison subjects who are exposed to antipsychotic medication for 15 days. This written report volition include upwardly to 40 healthy adult (21-fifty years old) volunteers. Participants will be recruited via online advertisements and flyers as well as budgeted healthy individuals who participated in previous studies. Investigators accept three aims: 1. to study the levels of chemicals and kinetics of enzymes associated with cellular energy metabolism in brain earlier and later on utilise of antipsychotic drug (using 1P MRS). 2. to collect data on the structure of the grayness affair and white matter; resting state functional brain activity; levels of encephalon chemicals including glutamate and GABA; and white matter integrity before and after use of antipsychotic drug (using structural MRI, fMRI, dTI, 1H MRS). iii. to investigate side effects of antipsychotic drugs. It was planed to give healthy participants a single 2.5 mg dose of olanzapine followed past a five mg dose for 14 days. Olanzapine, a second generation antipsychotic amanuensis, was selected to administer because this medication has potent effects on energy metabolism in general. The recommended daily dose range for olanzapine is indicated as 10-30 mg/d in the last "APA (American Psychiatric Association) Practice Guideline for the Treatment of Patients With Schizophrenia". A recent report suggests that minimum effective dose for olanzapine in schizophrenia is 7.v mg/d (the upper range of five mg ± 2.five mg/d) and college olanzapine doses (ten, ten ± 2.5, 15, and fifteen ± two.v mg/d) are more efficacious than placebo. Therefore information technology was determined to give good for you subjects merely 5 mg/d olanzapine, the lower limit of the optimal dose range (5 mg ± ii.v mg/d), to mimic the therapeutic effect merely also protect the participants from adverse effects of treatment. Equally the goal is to examine the effects of chronic drug use, the duration of medication was determined to be 15 days, the longest but historically safe olanzapine usage period in healthy individuals up to now. At that place is no published literature on the effects of olanzapine on brain measures. Therefore, it is not possible to calculate a sample size that would detect a given between-group difference in this report. Investigators plan to recruit a sample that is big enough to establish the absenteeism of a moderate or large effect. It was proposed that sample size of 30 subjects volition be sufficient to detect a deviation with effect sizes of 0.45 or greater as significant at the p<0.05 level with fourscore% power. Result sizes of 0.5 are generally considered moderate and 0.eight considered large. Therefore, a not-statistically significant finding with this sample size will suggest that any effects of olanzapine on encephalon metabolism are small at about. Investigators will collect interview and neuroimaging data at baseline and afterward the medication period. Deviations induced past the written report drug on good for you brain will be examined using paired t-tests for before and subsequently measurements. Investigation of parameters earlier and subsequently the use of antipsychotic drug in healthy people volition requite a risk to determine brain alterations related to drug itself, contained from the pathophysiology of the illness.
| Report Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 35 participants |
| Allotment: | N/A |
| Intervention Model: | Unmarried Group Consignment |
| Masking: | None (Open Label) |
| Main Purpose: | Basic Scientific discipline |
| Official Championship: | The Furnishings of Antipsychotic Drugs on Brain Metabolism in Healthy Individuals |
| Bodily Study Start Appointment : | Nov 17, 2017 |
| Actual Primary Completion Appointment : | November 8, 2019 |
| Actual Report Completion Date : | November 8, 2019 |
Resource links provided by the National Library of Medicine 
| Arm | Intervention/treatment |
|---|---|
| Experimental: 2nd Generation Antipsychotic Drug Olanzapine; a unmarried two.5 mg dose PO daily followed by 5 mg dose PO daily for 14 days | Drug: Olanzapine All subjects will have a unmarried 2.5 mg dose of olanzapine (Zyprexa Zydis) followed by a 5 mg dose for 14 days. (2.5 mg/d for 1 twenty-four hour period, 5 mg/d for 14 days). Other Proper noun: Zyprexa Zydis five mg tb |
Chief Outcome Measures :
- Change in Brain Nicotinamide Adenine Dinucleotide Metabolites NAD+/NADH [ Time Frame: Baseline and after 15 days medication period ]
Alter in brain nicotinamide adenine dinucleotide NAD+/NADH metabolite ratio as measured past in vivo 31P magnetic resonance spectroscopy
- Alter in Brain Phosphocreatine (PCr) [ Time Frame: Baseline and after 15 days medication period ]
Change in Phosphocreatine (PCr) metabolite concentration every bit measured by in vivo 31P magnetic resonance spectroscopy
- Change in Brain Creatine Kinase (CK) Forward Reaction Rate [ Fourth dimension Frame: Baseline and after 15 days medication period ]
Change in forwards reaction charge per unit abiding (kf) of the creatine kinase (CK) every bit measured by in vivo 31P magnetic resonance spectroscopy magnetization transfer
- Change in Brain Parenchymal pH [ Time Frame: baseline and after 15 days medication flow ]
Alter in encephalon parenchymal pH equally measured past in vivo 31P magnetic resonance spectroscopy
Secondary Outcome Measures :
- Modify in Volumes of the Frontal, Parietal and Temporal Lobe Regions [ Time Frame: baseline and after 15 twenty-four hour period medication period ]
Modify in the gray affair volumes (cubic millimeters) of the frontal, parietal and temporal lobes as defined past Freesurfer's Desikan-Killiany Brain Atlas. Information was caused using structural magnetic resonance imaging (MRI) at 3T.
- Change in Surface Expanse of the Frontal, Parietal and Temporal Regions [ Time Frame: baseline and after xv days medication period ]
Alter in the cortical surface area (millimeters squared) of the frontal, parietal and temporal lobes as defined by Freesurfer's Desikan-Killiany Encephalon Atlas. Data was acquired using structural magnetic resonance imaging (MRI) at 3T.
- Change in fMRI Resting State Functional Connectivity [ Fourth dimension Frame: baseline and later on 15 days medication catamenia ]
Change in resting land functional connectivity to the medial prefrontal cortex and superior parietal lobules following olanzapine administration period. Whole-brain, seed-to-voxel analyses were conducted utilizing anatomically-divers seed regions and age-corrected within-subjects f-tests were run to determine the presence and size (in voxels) of clusters where connectivity changed significantly following olanzapine administration. Results are reported in units of voxels for each cluster coming together a threshold of voxel-level uncorrected p<.001 and cluster-level p-FDR<.05. A upshot of goose egg indicates that no clusters were identified inside subjects as changed in connectivity relative to the seed regions.
- Alter in GABA Concentration [ Time Frame: baseline and afterwards 15 days medication period ]
Change in GABA concentration measured by proton magnetic resonance spectroscopy.
- Alter in Fractional Anisotropy (FA) Measured by Diffusion Tensor Imaging (DTI) [ Time Frame: baseline and afterwards 15 days medication menstruation ]
Change in fractional anisotropy (FA), a scalar measure out of diffusivity, of h2o in the brain assessed past DTI at 3T. FA values range from 0 (isotropic, meaning diffusion is as restricted in 3D space) to ane (anisotrophic, meaning that improvidence is completely restricted to a single management).
- Change in Glutamate Metabolite Concentration [ Time Frame: baseline and afterwards fifteen days medication period ]
Change in glutamate metabolite concentration measured by proton magnetic resonance spectroscopy.
- Change in MATRICS Cerebral Consensus Battery (MCCB) Total Composite Score [ Fourth dimension Frame: baseline and after fifteen days medication period ]
Change in the MATRICS Cognitive Consensus Battery (MCCB), that includes 10 tasks that measure processing speed (Cursory Assessment of Cognition in Schizophrenia - Symbol Coding, Beast Fluency, Trails A), attention (Continuous Functioning Test), working memory (WMS-III Spatial Span, Letter of the alphabet-Number Span), verbal learning (Hopkins Verbal Learning Test - Revised), visual learning (Brief Visuospatial Memory Exam - Revised), problem solving (Neuropsychological Assessment Battery Mazes) and social cognition (Mayer-Salovey-Caruso Emotional Intelligence Test). Scores from each subtest are normed and their T-scores are summed to yield a MCCB composite score, then the total composite T-score is standardized to normative data among a salubrious population. The composite T-score has a hateful of fifty and a standard divergence of 10. College total composite scores indicate better cognitive outcomes.
Other Outcome Measures:
- Change in Montgomery-Asberg Low Rating Scale (MADRS) Score [ Time Frame: baseline and later on 15 days medication period ]
Modify in Montgomery-Asberg Low Rating Scale (MADRS) score, a 0-sixty point scale rating depressive symptoms. Higher scores indicate more astringent clinical symptoms.
- Change in Beck Depression Inventory (BDI) Score [ Time Frame: baseline and afterwards 15 days medication period ]
Alter in Beck Depression Inventory (BDI) score, a self-report questionnaire measuring depressive symptoms on a scale of 0-63. Scores ranging 0-9 generally betoken minimal depressive symptoms, while scores x-18 bespeak mild, xix-29 indicates moderate, and 30-63 indicates severe depressive symptoms, respectively.
- Change in Young Mania Rating Scale (YMRS) Score [ Time Frame: baseline and after 15 days medication period ]
Change in Young Mania Rating Scale (YMRS) score, an interview-based, eleven-detail calibration that measures the severity of core features of clinical mania. 7 items are scored on a 0-4 point calibration, while the remaining 4 are scored on a 0-8 betoken scale, for a total possible range of 0-64. Higher scores indicate more severe manic symptoms.
- Alter in Brook Anxiety Inventory (BAI) Score [ Time Frame: baseline and later 15 days medication flow ]
Change in Beck Anxiety Inventory (BAI) score, a self-study measure out of anxiety symptoms. Scores range from 0-63, with college scores indicating more severe anxiety.
- Modify in The Columbia Suicide Severity Rating Scale Score [ Fourth dimension Frame: baseline and 2, v, 10, 15 days during medication period ]
Modify in The Columbia Suicide Severity Rating Scale score, a cocky-written report calibration measuring suicidality. Only the total score, non subscale of suicidal ideation intensity, volition be measured. Total scores can range from 0-10, with higher scores indicating increased suicidality.
- Modify in Pittsburgh Slumber Quality Index Score [ Fourth dimension Frame: baseline and after 15 days medication menstruum ]
Modify in Pittsburgh Sleep Quality Index score, a measurement of sleep quality. The index measures 7 sleep components on a 0-3 scale; each of the 7 raw scores is summed to get a global score. The global score ranges from 0-21, with higher scores indicating poor sleep quality. Scores >v are typically considered poor sleep quality.
- Change in LUNSERS (Liverpool University Neuroleptic Side Effect Rating Scale) Score [ Time Frame: baseline and two, 5, 10 and 15 days (or final assessment) during medication menstruum ]
Change in LUNSERS (Liverpool University Neuroleptic Side Consequence Rating Scale) score, a self-report measure of antipsychotic side effects. The scale has 51 questions, 41 of which are about side-effects and 10 "ruddy herrings" for validation purposes. The total neuroleptic side effect score is derived from the sum of the 41 side-effect questions, with a potential range of 0-164. Higher scores bespeak more than astringent neuroleptic side effects.
- Modify in Trunk Weight [ Time Frame: baseline and 2, 5, 10 and 15 days (or final assessment) during medication menstruum ]
Change in participant torso weight in kg, every bit measured using a standing scale.
- Change in Hip Circumference [ Time Frame: baseline and 2, 5, x and 15 days (or final assessment) during medication menstruum ]
Modify in the hip circumference measurement, taken as an boilerplate of 3 measures by record measure
- Change in Waist Circumference [ Fourth dimension Frame: baseline and 2, 5, 10 and 15 days (or final assessment) during medication period ]
Change in waist circumference measurements, taken as an average of 3 measures by tape measure.
- Change in Claret Glucose Levels [ Fourth dimension Frame: baseline and after 15 days during medication flow ]
Modify in fasting serum glucose levels.
- Modify in Fasting Total Cholesterol Level [ Time Frame: baseline and after fifteen days medication period ]
Change in fasting total cholesterol level
- Change in Hemoglobin A1c Level [ Time Frame: baseline and after 15 days medication period ]
Change in fasting, Hemoglobin A1c level
- Modify in Serum Insulin Levels [ Time Frame: baseline and after xv days medication menses ]
Modify in insulin fasting serum levels
- Change in Prolactin Levels [ Time Frame: baseline and after 15 days medication catamenia ]
Change prolactin serum levels
- Change in Full Caloric Intake [ Time Frame: baseline and subsequently fifteen days medication period ]
Alter in total caloric intake every bit assessed past the ASA24 Dietary Call back and Food Frequency Questionnaire - Revised. The ASA24 is a self-administered 24-hour dietary recollect assessment.
- Change in The Wisconsin Schizotypy Scales - Short Class Scores [ Fourth dimension Frame: baseline and after 15 days medication period ]
Change in Wisconsin Schizotypy Scales (WSS) Brusk Form score, a self-report questionnaire assessing schizotypy in clinical and non-clinical samples. The mensurate has four scales, each with xv Truthful/False questions. In that location are 13 crimson-herring questions, that, if answered "True" invalidate the examination. Each "faux" response is scored 0, and each "true" response is scored one. Scores for each calibration range from 0 - 15, with higher scores indicating greater schizotypy. The WSS positive schizotypy score consists of the summed score of the perceptual aberration and magical ideation scales and scores range from 0-30, with higher scores indicating greater positive schizotypy. The WSS negative schizotypy score sums scores from the physical anhedonia and social anhedonia scales and ranges from 0-30, with college scores indicating greater negative schizotypy.
- Change in the Early Psychosis Social Scale Survey Score [ Time Frame: baseline and after 15 days medication menstruation ]
Change in the Early Psychosis Social Scale score item of missed absences from school or work. Scores range from ane-5, with higher scores indicating more absences from school or work.
- Change in the Prodromal Questionnaire, Brief Version Total Score [ Time Frame: baseline and after fifteen days medication period ]
Change in the Prodromal Questionnaire, Brief Version score, a 21 particular self-report questionnaire designed to aid identify those at ultra-high risk for developing psychotic symptoms. The total score is derived every bit the sum of all 21 items, with a possible range of 0-21. College scores indicate greater psychopathology.
- Change in the Symptoms Checklist - 90 - Revised Global Severity Score [ Time Frame: baseline and afterward 15 days medication menstruum ]
Changes in the Symptoms Checklist - ninety - Revised calibration, which measures 9 domains of psychological dysfunction, summing to create an overall psychological distress (Global Severity Score). The scores of each of the ix domains - somatization, obsessive-compulsive, interpersonal sensitivity, low, anxiety, hostility, phobic anxiety, paranoid ideation and psychoticism - combine for a total of 90 items, each measured on a five-bespeak calibration. The sums of all xc detail scores, ranging 0-360, creates the Global Severity score. Higher scores signal greater psychopathology.
- Modify in the Country-Trait Anxiety Inventory for Adults Scores [ Time Frame: baseline and after fifteen days medication period ]
Alter in the State-Trait Anxiety Inventory for Adults, which measures both state and trait anxiety using 2 subscales for a full of forty items. Each subscale has a range of 20-80, with higher scores indicating greater state or trait anxiety, respectively.
- Change in the Earth Health Organization Quality of Life Questionnaire Score [ Time Frame: baseline and after 15 days medication catamenia ]
Modify in the World Health Organization Quality of Life questionnaire score, a 26-particular assessment of overall quality of life. The questionnaire encompasses 4 domains: physical health, psychological health, social relationships, and environment. In that location are ii additional questions, which assess the participant's perceptions of their own quality of life and physical wellness. Higher scores point amend quality of life. Scores are summed within each domain. Total score is obtained by transforming for a full range of 0-100 within each domain.
Information from the National Library of Medicine
Choosing to participate in a study is an of import personal decision. Talk with your doc and family members or friends about deciding to join a study. To larn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn Most Clinical Studies.
| Ages Eligible for Written report: | 21 Years to fifty Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Age: 21-fifty years former
- Male or female
- Without psychiatric diagnosis according to a structured psychiatric interview (SCID)
- Without history of a psychotic disorder amongst parents, siblings, or children
Exclusion Criteria:
- Significant medical or neurological illness
- Diagnosis diabetes mellitus, uncontrolled hypertension, severe hypotension, coronary artery illness, metabolic syndrome, glaucoma, liver impairment, decreased renal function, respiratory disorders, peptic ulcer disease (absolute and relative contraindications to use of antipsychotic drugs)
- Body mass index (BMI) over 30
- Taking whatever other medications, including over the counter supplements with the exception of oral contraceptives for women
- Pregnancy. Females of child-bearing age must be using an effective contraceptive method
- History of smoking, substance abuse or dependence
- Contraindication to MR scan (claustrophobia, cardiac pacemakers, metallic clips and stents on blood vessels, 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 metallic filings, other metallic surgical hardware in vital areas, sure tattoos with metallic ink, certain transdermal patches, metal-containing IUDs)
- Medical status that would prevent claret draws
Information from the National Library of Medicine
To acquire more about this study, you or your dr. may contact the report enquiry staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02536846
| United states, Massachusetts | |
| McLean Infirmary | |
| Belmont, Massachusetts, United States, 02478 | |
Dost Ongur
| Principal Investigator: | Dost Ongur, MD, PhD | Mclean Hospital |
Documents provided by Dost Ongur, Mclean Hospital:
Agostinho FR, Réus GZ, Stringari RB, Ribeiro KF, Ferraro AK, Benedet J, Rochi North, Scaini G, Streck EL, Quevedo J. Handling with olanzapine, fluoxetine and olanzapine/fluoxetine alters citrate synthase action in rat encephalon. Neurosci Lett. 2011 Jan x;487(three):278-81. doi: 10.1016/j.neulet.2010.x.037. Epub 2010 Oct 28.
| Responsible Party: | Dost Ongur, Principal of Psychotic Disorders Segmentation at McLean Hospital and Associate Professor in Psychiatry at Harvard Medical School, Mclean Hospital |
| ClinicalTrials.gov Identifier: | NCT02536846 |
| Other Study ID Numbers: | 2015P001140 041512 ( Other Grant/Funding Number: McLean Hospital ) |
| First Posted: | September 1, 2015 Fundamental Record Dates |
| Results First Posted: | August 12, 2021 |
| Last Update Posted: | Baronial 12, 2021 |
| Final Verified: | July 2021 |
| Studies a U.S. FDA-regulated Drug Product: | Yep |
| Studies a U.S. FDA-regulated Device Production: | No |
Keywords provided past Dost Ongur, Mclean Hospital:
| Healthy volunteers antipsychotic drugs encephalon metabolism |
Boosted relevant MeSH terms:
| Olanzapine Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Antipsychotic Agents Tranquilizing Agents | Key Nervous System Depressants Psychotropic Drugs Serotonin Uptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Activity Neurotransmitter Agents Serotonin Agents |
Source: https://clinicaltrials.gov/ct2/show/NCT02536846
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