What Do Antipsychotics Do to a Normal Person
Brief Summary:
The primary aim of this written report is to investigate antipsychotic drug effects on good for you brain metabolism.
| Status or illness | Intervention/handling | Phase |
|---|---|---|
| Healthy | Drug: Olanzapine | Phase 4 |
Detailed Clarification:
Schizophrenia is a complex psychiatric disorder characterized by alterations in brain structure. 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 recent years accumulating evidence suggests that exposure to the furnishings of psychotropic drugs may contribute to the structural and other changes in brain. Therefore, employ of antipsychotic medications as handling for schizophrenia represents a potential confounding gene in many of the studies. Near neuroimaging studies of schizophrenia to date take non included the examination of non-medicated patients, making conclusions almost medication effects on neuroimaging measures difficult. MRI studies of structural brain changes across time are express past the fact that due to ethical reasons neither untreated subjects with schizophrenia nor control subjects exposed to antipsychotic medications can be used every bit comparison groups. There are some preclinical rat and primate models which revealed chronic antipsychotic-induced alterations in the brain. Withal few studies investigate the furnishings of chronic exposure to antipsychotic drugs on healthy human brain. Therefore in this study, investigators aimed to evaluate brain alterations induced by chronic drug exposure in salubrious volunteers. To address this problem, nosotros volition conduct a single-site, unmarried arm, open-label, interventional, multimodal neuroimaging report of salubrious comparison subjects who are exposed to antipsychotic medication for xv days. This study will include up to forty salubrious adult (21-l years onetime) volunteers. Participants will exist recruited via online advertisements and flyers besides equally approaching healthy individuals who participated in previous studies. Investigators have iii aims: 1. to written report the levels of chemicals and kinetics of enzymes associated with cellular free energy metabolism in brain before and later on use of antipsychotic drug (using 1P MRS). ii. to collect data on the structure of the gray matter and white matter; resting country functional encephalon activeness; levels of brain chemicals including glutamate and GABA; and white matter integrity earlier and after use of antipsychotic drug (using structural MRI, fMRI, dTI, 1H MRS). three. to investigate side effects of antipsychotic drugs. Information technology was planed to requite healthy participants a unmarried 2.5 mg dose of olanzapine followed by a five mg dose for 14 days. Olanzapine, a 2d generation antipsychotic agent, was selected to administer because this medication has strong 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) Do Guideline for the Treatment of Patients With Schizophrenia". A recent study suggests that minimum effective dose for olanzapine in schizophrenia is 7.5 mg/d (the upper range of 5 mg ± ii.five mg/d) and higher olanzapine doses (x, 10 ± two.5, xv, and fifteen ± two.v mg/d) are more efficacious than placebo. Therefore it was determined to give healthy subjects only v mg/d olanzapine, the lower limit of the optimal dose range (5 mg ± 2.v mg/d), to mimic the therapeutic effect but also protect the participants from adverse effects of treatment. As the goal is to examine the furnishings of chronic drug use, the duration of medication was adamant to be 15 days, the longest but historically safe olanzapine usage menses in salubrious individuals up to at present. At that place is no published literature on the effects of olanzapine on encephalon measures. Therefore, it is not possible to calculate a sample size that would detect a given betwixt-group difference in this study. Investigators plan to recruit a sample that is big enough to plant the absence of a moderate or large effect. It was proposed that sample size of 30 subjects volition be sufficient to detect a difference with effect sizes of 0.45 or greater as significant at the p<0.05 level with lxxx% power. Effect sizes of 0.5 are generally considered moderate and 0.viii considered big. Therefore, a non-statistically meaning finding with this sample size will suggest that any effects of olanzapine on brain metabolism are minor at nigh. Investigators will collect interview and neuroimaging data at baseline and after the medication catamenia. Deviations induced by the study drug on good for you brain will be examined using paired t-tests for before and after measurements. Investigation of parameters earlier and afterwards the use of antipsychotic drug in healthy people will requite a hazard to decide brain alterations related to drug itself, independent from the pathophysiology of the disease.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 35 participants |
| Allotment: | North/A |
| Intervention Model: | Unmarried Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Basic Scientific discipline |
| Official Championship: | The Furnishings of Antipsychotic Drugs on Encephalon Metabolism in Healthy Individuals |
| Bodily Study Start Date : | November 17, 2017 |
| Actual Primary Completion Date : | Nov viii, 2019 |
| Bodily Report Completion Date : | November 8, 2019 |
Resource links provided by the National Library of Medicine 
| Arm | Intervention/treatment |
|---|---|
| Experimental: Second Generation Antipsychotic Drug Olanzapine; a single 2.5 mg dose PO daily followed by 5 mg dose PO daily for 14 days | Drug: Olanzapine All subjects volition take a single two.five mg dose of olanzapine (Zyprexa Zydis) followed by a 5 mg dose for xiv days. (ii.v mg/d for 1 twenty-four hour period, five mg/d for xiv days). Other Name: Zyprexa Zydis five mg tb |
Primary Outcome Measures :
- Alter in Brain Nicotinamide Adenine Dinucleotide Metabolites NAD+/NADH [ Time Frame: Baseline and after xv days medication menses ]
Change in encephalon nicotinamide adenine dinucleotide NAD+/NADH metabolite ratio equally measured by in vivo 31P magnetic resonance spectroscopy
- Modify in Brain Phosphocreatine (PCr) [ Time Frame: Baseline and after 15 days medication menses ]
Change in Phosphocreatine (PCr) metabolite concentration every bit measured by in vivo 31P magnetic resonance spectroscopy
- Change in Brain Creatine Kinase (CK) Forward Reaction Charge per unit [ Time Frame: Baseline and after xv days medication flow ]
Modify in forward reaction charge per unit constant (kf) of the creatine kinase (CK) equally measured by in vivo 31P magnetic resonance spectroscopy magnetization transfer
- Change in Brain Parenchymal pH [ Time Frame: baseline and after 15 days medication period ]
Change in brain parenchymal pH equally measured by in vivo 31P magnetic resonance spectroscopy
Secondary Effect Measures :
- Change in Volumes of the Frontal, Parietal and Temporal Lobe Regions [ Time Frame: baseline and after 15 day medication flow ]
Change in the gray matter volumes (cubic millimeters) of the frontal, parietal and temporal lobes as defined by Freesurfer'south Desikan-Killiany Encephalon Atlas. Data was acquired using structural magnetic resonance imaging (MRI) at 3T.
- Change in Surface Area of the Frontal, Parietal and Temporal Regions [ Time Frame: baseline and after xv days medication period ]
Change in the cortical surface expanse (millimeters squared) of the frontal, parietal and temporal lobes as defined past Freesurfer's Desikan-Killiany Encephalon Atlas. Data was acquired using structural magnetic resonance imaging (MRI) at 3T.
- Change in fMRI Resting State Functional Connectivity [ Time Frame: baseline and after 15 days medication period ]
Change in resting state functional connectivity to the medial prefrontal cortex and superior parietal lobules post-obit olanzapine administration menstruation. Whole-brain, seed-to-voxel analyses were conducted utilizing anatomically-defined 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 post-obit 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 outcome of zippo indicates that no clusters were identified inside subjects as changed in connectivity relative to the seed regions.
- Change in GABA Concentration [ Time Frame: baseline and afterward fifteen days medication menstruation ]
Alter in GABA concentration measured by proton magnetic resonance spectroscopy.
- Change in Fractional Anisotropy (FA) Measured by Improvidence Tensor Imaging (DTI) [ Time Frame: baseline and after xv days medication menses ]
Change in fractional anisotropy (FA), a scalar measure out of diffusivity, of water in the encephalon assessed by DTI at 3T. FA values range from 0 (isotropic, meaning improvidence is as restricted in 3D space) to 1 (anisotrophic, pregnant that diffusion is completely restricted to a single direction).
- Change in Glutamate Metabolite Concentration [ Fourth dimension Frame: baseline and after 15 days medication menstruum ]
Change in glutamate metabolite concentration measured by proton magnetic resonance spectroscopy.
- Alter in MATRICS Cognitive Consensus Bombardment (MCCB) Total Composite Score [ Time Frame: baseline and after 15 days medication catamenia ]
Change in the MATRICS Cerebral Consensus Battery (MCCB), that includes 10 tasks that mensurate processing speed (Brief Cess of Cognition in Schizophrenia - Symbol Coding, Animal Fluency, Trails A), attention (Continuous Performance Examination), working retentivity (WMS-3 Spatial Bridge, Letter-Number Span), verbal learning (Hopkins Verbal Learning Examination - Revised), visual learning (Brief Visuospatial Memory Test - Revised), trouble 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, and then the full composite T-score is standardized to normative data among a healthy population. The blended T-score has a mean of 50 and a standard divergence of 10. Higher total blended scores indicate better cognitive outcomes.
Other Outcome Measures:
- Modify in Montgomery-Asberg Low Rating Scale (MADRS) Score [ Time Frame: baseline and later on 15 days medication menstruum ]
Modify in Montgomery-Asberg Depression Rating Scale (MADRS) score, a 0-60 point scale rating depressive symptoms. Higher scores betoken more than severe clinical symptoms.
- Change in Beck Depression Inventory (BDI) Score [ Time Frame: baseline and after 15 days medication period ]
Change in Beck Low Inventory (BDI) score, a self-written report questionnaire measuring depressive symptoms on a scale of 0-63. Scores ranging 0-9 more often than not indicate minimal depressive symptoms, while scores x-18 indicate mild, xix-29 indicates moderate, and xxx-63 indicates severe depressive symptoms, respectively.
- Modify in Young Mania Rating Calibration (YMRS) Score [ Fourth dimension Frame: baseline and after 15 days medication period ]
Change in Young Mania Rating Scale (YMRS) score, an interview-based, 11-item scale that measures the severity of core features of clinical mania. 7 items are scored on a 0-four signal scale, while the remaining 4 are scored on a 0-viii point scale, for a total possible range of 0-64. College scores indicate more severe manic symptoms.
- Change in Beck Feet Inventory (BAI) Score [ Fourth dimension Frame: baseline and after 15 days medication period ]
Change in Beck Anxiety Inventory (BAI) score, a cocky-study measure of feet symptoms. Scores range from 0-63, with college scores indicating more severe anxiety.
- Modify in The Columbia Suicide Severity Rating Scale Score [ Time Frame: baseline and 2, five, 10, 15 days during medication catamenia ]
Change in The Columbia Suicide Severity Rating Scale score, a self-report scale measuring suicidality. Only the full score, not subscale of suicidal ideation intensity, volition be measured. Total scores can range from 0-10, with college scores indicating increased suicidality.
- Change in Pittsburgh Sleep Quality Index Score [ Time Frame: baseline and afterward 15 days medication period ]
Modify in Pittsburgh Sleep Quality Index score, a measurement of sleep quality. The index measures 7 slumber components on a 0-3 calibration; each of the 7 raw scores is summed to go a global score. The global score ranges from 0-21, with college scores indicating poor sleep quality. Scores >5 are typically considered poor sleep quality.
- Change in LUNSERS (Liverpool Academy Neuroleptic Side Outcome Rating Scale) Score [ Time Frame: baseline and 2, 5, 10 and 15 days (or final assessment) during medication menstruum ]
Change in LUNSERS (Liverpool Academy Neuroleptic Side Effect Rating Calibration) score, a self-report measure of antipsychotic side effects. The scale has 51 questions, 41 of which are about side-effects and ten "red herrings" for validation purposes. The full neuroleptic side effect score is derived from the sum of the 41 side-effect questions, with a potential range of 0-164. Higher scores betoken more severe neuroleptic side effects.
- Alter in Trunk Weight [ Fourth dimension Frame: baseline and 2, 5, 10 and 15 days (or terminal assessment) during medication menses ]
Change in participant torso weight in kg, as measured using a standing scale.
- Change in Hip Circumference [ Time Frame: baseline and 2, v, 10 and 15 days (or concluding assessment) during medication catamenia ]
Modify in the hip circumference measurement, taken as an average of 3 measures by tape measure
- Change in Waist Circumference [ Fourth dimension Frame: baseline and 2, 5, ten and 15 days (or last assessment) during medication menstruation ]
Change in waist circumference measurements, taken equally an average of 3 measures by record measure.
- Change in Blood Glucose Levels [ Time Frame: baseline and after 15 days during medication menstruation ]
Change in fasting serum glucose levels.
- Change in Fasting Total Cholesterol Level [ Fourth dimension Frame: baseline and after 15 days medication period ]
Change in fasting total cholesterol level
- Alter in Hemoglobin A1c Level [ Time Frame: baseline and subsequently 15 days medication period ]
Modify in fasting, Hemoglobin A1c level
- Modify in Serum Insulin Levels [ Time Frame: baseline and subsequently fifteen days medication period ]
Modify in insulin fasting serum levels
- Modify in Prolactin Levels [ Fourth dimension Frame: baseline and later 15 days medication period ]
Alter prolactin serum levels
- Alter in Total Caloric Intake [ Time Frame: baseline and after 15 days medication period ]
Change in total caloric intake equally assessed past the ASA24 Dietary Retrieve and Nutrient Frequency Questionnaire - Revised. The ASA24 is a self-administered 24-hour dietary think assessment.
- Change in The Wisconsin Schizotypy Scales - Short Class Scores [ Fourth dimension Frame: baseline and subsequently xv days medication catamenia ]
Alter in Wisconsin Schizotypy Scales (WSS) Brusque Form score, a self-report questionnaire assessing schizotypy in clinical and non-clinical samples. The measure has four scales, each with 15 True/Simulated questions. In that location are 13 ruddy-herring questions, that, if answered "True" invalidate the test. Each "false" response is scored 0, and each "true" response is scored one. Scores for each scale 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-xxx, 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-xxx, with college scores indicating greater negative schizotypy.
- Modify in the Early Psychosis Social Scale Survey Score [ Fourth dimension Frame: baseline and later on 15 days medication menstruum ]
Change in the Early Psychosis Social Scale score item of missed absences from school or work. Scores range from one-five, with higher scores indicating more than 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 detail self-study questionnaire designed to assist identify those at ultra-high risk for developing psychotic symptoms. The total score is derived as the sum of all 21 items, with a possible range of 0-21. Higher scores indicate greater psychopathology.
- Change in the Symptoms Checklist - 90 - Revised Global Severity Score [ Time Frame: baseline and after 15 days medication menstruation ]
Changes in the Symptoms Checklist - 90 - Revised scale, which measures 9 domains of psychological dysfunction, summing to create an overall psychological distress (Global Severity Score). The scores of each of the nine domains - somatization, obsessive-compulsive, interpersonal sensitivity, depression, feet, hostility, phobic anxiety, paranoid ideation and psychoticism - combine for a total of ninety items, each measured on a five-point scale. The sums of all 90 item scores, ranging 0-360, creates the Global Severity score. Higher scores signal greater psychopathology.
- Change in the State-Trait Anxiety Inventory for Adults Scores [ Time Frame: baseline and afterward 15 days medication catamenia ]
Alter in the State-Trait Feet Inventory for Adults, which measures both country and trait anxiety using 2 subscales for a total of xl items. Each subscale has a range of twenty-80, with higher scores indicating greater state or trait anxiety, respectively.
- Modify in the World Wellness Arrangement Quality of Life Questionnaire Score [ Time Frame: baseline and later on 15 days medication period ]
Modify in the World Wellness Organization Quality of Life questionnaire score, a 26-item assessment of overall quality of life. The questionnaire encompasses 4 domains: physical wellness, psychological health, social relationships, and environs. In that location are ii additional questions, which assess the participant'southward perceptions of their own quality of life and physical health. College scores indicate better quality of life. Scores are summed within each domain. Total score is obtained by transforming for a total range of 0-100 within each domain.
Information from the National Library of Medicine
Choosing to participate in a written report is an important personal decision. Talk with your md and family unit members or friends most deciding to join a study. To acquire more about this report, you or your medico may contact the study research staff using the contacts provided beneath. For general data, Learn Well-nigh Clinical Studies.
| Ages Eligible for Report: | 21 Years to 50 Years (Adult) |
| Sexes Eligible for Report: | All |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Age: 21-50 years old
- Male person or female
- Without psychiatric diagnosis co-ordinate to a structured psychiatric interview (SCID)
- Without history of a psychotic disorder among parents, siblings, or children
Exclusion Criteria:
- Pregnant medical or neurological illness
- Diagnosis diabetes mellitus, uncontrolled hypertension, severe hypotension, coronary artery illness, metabolic syndrome, glaucoma, liver damage, decreased renal office, respiratory disorders, peptic ulcer affliction (absolute and relative contraindications to use of antipsychotic drugs)
- Body mass index (BMI) over xxx
- Taking any other medications, including over the counter supplements with the exception of oral contraceptives for women
- Pregnancy. Females of child-begetting historic period must exist using an constructive contraceptive method
- History of smoking, substance abuse or dependence
- Contraindication to MR browse (claustrophobia, cardiac pacemakers, metal clips and stents on claret vessels, bogus center valves, bogus arms, hands, legs, etc., brain stimulator devices, implanted drug pumps, ear implants, centre implants or known metallic fragments in eyes, exposure to shrapnel or metal filings, other metallic surgical hardware in vital areas, certain tattoos with metallic ink, certain transdermal patches, metal-containing IUDs)
- Medical condition that would forbid blood draws
Data from the National Library of Medicine
To learn more about this study, yous or your doctor may contact the written report research 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 Hospital | |
| Belmont, Massachusetts, Usa, 02478 | |
Dost Ongur
| Principal Investigator: | Dost Ongur, MD, PhD | Mclean Hospital |
Documents provided past Dost Ongur, Mclean Infirmary:
Agostinho FR, Réus GZ, Stringari RB, Ribeiro KF, Ferraro AK, Benedet J, Rochi N, Scaini G, Streck EL, Quevedo J. Treatment with olanzapine, fluoxetine and olanzapine/fluoxetine alters citrate synthase activity in rat brain. Neurosci Lett. 2011 Jan ten;487(3):278-81. doi: 10.1016/j.neulet.2010.10.037. Epub 2010 October 28.
| Responsible Party: | Dost Ongur, Chief of Psychotic Disorders Division at McLean Infirmary and Associate Professor in Psychiatry at Harvard Medical School, Mclean Hospital |
| ClinicalTrials.gov Identifier: | NCT02536846 |
| Other Report ID Numbers: | 2015P001140 041512 ( Other Grant/Funding Number: McLean Hospital ) |
| First Posted: | September 1, 2015 Central Tape Dates |
| Results First Posted: | August 12, 2021 |
| Last Update Posted: | Baronial 12, 2021 |
| Last Verified: | July 2021 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.Southward. FDA-regulated Device Product: | No |
Keywords provided past Dost Ongur, Mclean Infirmary:
| Good for you volunteers antipsychotic drugs brain metabolism |
Additional relevant MeSH terms:
| Olanzapine Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Antipsychotic Agents Tranquilizing Agents | Central Nervous Organisation Depressants Psychotropic Drugs Serotonin Uptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Activeness Neurotransmitter Agents Serotonin Agents |
Source: https://clinicaltrials.gov/ct2/show/NCT02536846
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