The Effects of Antipsychotic Drugs on Brain Metabolism in Healthy Individuals

NCT02536846 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: 2015P001140041512
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of this study is to investigate antipsychotic drug effects on healthy brain metabolism.

Conditions

Healthy

Keywords

Healthy volunteers; antipsychotic drugs; brain metabolism

Outcome Measures

Primary Outcomes (4)

• Change in Brain Nicotinamide Adenine Dinucleotide Metabolites NAD+/NADH

  Change in brain nicotinamide adenine dinucleotide NAD+/NADH metabolite ratio as measured by in vivo 31P magnetic resonance spectroscopy

  Baseline and after 15 days medication period

• Change in Brain Phosphocreatine (PCr)

  Change in Phosphocreatine (PCr) metabolite concentration as measured by in vivo 31P magnetic resonance spectroscopy

  Baseline and after 15 days medication period

• Change in Brain Creatine Kinase (CK) Forward Reaction Rate

  Change in forward reaction rate constant (kf) of the creatine kinase (CK) as measured by in vivo 31P magnetic resonance spectroscopy magnetization transfer

  Baseline and after 15 days medication period

• Change in Brain Parenchymal pH

  Change in brain parenchymal pH as measured by in vivo 31P magnetic resonance spectroscopy

  baseline and after 15 days medication period

Secondary Outcomes (7)

• Change in Volumes of the Frontal, Parietal and Temporal Lobe Regions

  baseline and after 15 day medication period

• Change in Surface Area of the Frontal, Parietal and Temporal Regions

  baseline and after 15 days medication period

• Change in fMRI Resting State Functional Connectivity

  baseline and after 15 days medication period

• Change in GABA Concentration

  baseline and after 15 days medication period

• Change in Fractional Anisotropy (FA) Measured by Diffusion Tensor Imaging (DTI)

  baseline and after 15 days medication period

Other Outcomes (22)

• Change in Montgomery-Asberg Depression Rating Scale (MADRS) Score

  baseline and after 15 days medication period

• Change in Beck Depression Inventory (BDI) Score

  baseline and after 15 days medication period

• Change in Young Mania Rating Scale (YMRS) Score

  baseline and after 15 days medication period

Study Arms (1)

Second Generation Antipsychotic Drug

EXPERIMENTAL

Olanzapine; a single 2.5 mg dose PO daily followed by 5 mg dose PO daily for 14 days

Drug: Olanzapine

Interventions

Olanzapine DRUG

All subjects will take a single 2.5 mg dose of olanzapine (Zyprexa Zydis) followed by a 5 mg dose for 14 days. (2.5 mg/d for 1 day, 5 mg/d for 14 days).

Also known as: Zyprexa Zydis 5 mg tb

Second Generation Antipsychotic Drug

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 21-50 years old
• Male or female
• Without psychiatric diagnosis according to a structured psychiatric interview (SCID)
• Without history of a psychotic disorder among parents, siblings, or children

You may not qualify if:

• Significant medical or neurological illness
• Diagnosis diabetes mellitus, uncontrolled hypertension, severe hypotension, coronary artery disease, 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 any 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, metal 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 metal filings, other metallic surgical hardware in vital areas, certain tattoos with metallic ink, certain transdermal patches, metal-containing IUDs)
• Medical condition that would prevent blood draws

Sponsors & Collaborators

• Dost Ongur: lead

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

Related Publications (13)

• Martinez ZA, Oostwegel J, Geyer MA, Ellison GD, Swerdlow NR. "Early" and "late" effects of sustained haloperidol on apomorphine- and phencyclidine-induced sensorimotor gating deficits. Neuropsychopharmacology. 2000 Nov;23(5):517-27. doi: 10.1016/S0893-133X(00)00147-0.

  PMID: 11027917 BACKGROUND

• Agostinho FR, Reus 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 10;487(3):278-81. doi: 10.1016/j.neulet.2010.10.037. Epub 2010 Oct 28.

  PMID: 20971158 BACKGROUND

• Dorph-Petersen KA, Pierri JN, Perel JM, Sun Z, Sampson AR, Lewis DA. The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys. Neuropsychopharmacology. 2005 Sep;30(9):1649-61. doi: 10.1038/sj.npp.1300710.

  PMID: 15756305 BACKGROUND

• Konopaske GT, Dorph-Petersen KA, Pierri JN, Wu Q, Sampson AR, Lewis DA. Effect of chronic exposure to antipsychotic medication on cell numbers in the parietal cortex of macaque monkeys. Neuropsychopharmacology. 2007 Jun;32(6):1216-23. doi: 10.1038/sj.npp.1301233. Epub 2006 Oct 25.

  PMID: 17063154 BACKGROUND

• Konopaske GT, Dorph-Petersen KA, Sweet RA, Pierri JN, Zhang W, Sampson AR, Lewis DA. Effect of chronic antipsychotic exposure on astrocyte and oligodendrocyte numbers in macaque monkeys. Biol Psychiatry. 2008 Apr 15;63(8):759-65. doi: 10.1016/j.biopsych.2007.08.018. Epub 2007 Oct 22.

  PMID: 17945195 BACKGROUND

• Vita A, De Peri L. The effects of antipsychotic treatment on cerebral structure and function in schizophrenia. Int Rev Psychiatry. 2007 Aug;19(4):429-36. doi: 10.1080/09540260701486332.

  PMID: 17671875 BACKGROUND

• Smieskova R, Fusar-Poli P, Allen P, Bendfeldt K, Stieglitz RD, Drewe J, Radue EW, McGuire PK, Riecher-Rossler A, Borgwardt SJ. The effects of antipsychotics on the brain: what have we learnt from structural imaging of schizophrenia?--a systematic review. Curr Pharm Des. 2009;15(22):2535-49. doi: 10.2174/138161209788957456.

  PMID: 19689326 BACKGROUND

• Leucht S, Samara M, Heres S, Patel MX, Woods SW, Davis JM. Dose equivalents for second-generation antipsychotics: the minimum effective dose method. Schizophr Bull. 2014 Mar;40(2):314-26. doi: 10.1093/schbul/sbu001. Epub 2014 Feb 3.

  PMID: 24493852 BACKGROUND

• Vidarsdottir S, Roelfsema F, Frolich M, Pijl H. Olanzapine shifts the temporal relationship between the daily acrophase of serum prolactin and cortisol concentrations rhythm in healthy men. Psychoneuroendocrinology. 2009 Jun;34(5):705-12. doi: 10.1016/j.psyneuen.2008.11.008. Epub 2009 Jan 7.

  PMID: 19131173 BACKGROUND

• Vidarsdottir S, de Leeuw van Weenen JE, Frolich M, Roelfsema F, Romijn JA, Pijl H. Effects of olanzapine and haloperidol on the metabolic status of healthy men. J Clin Endocrinol Metab. 2010 Jan;95(1):118-25. doi: 10.1210/jc.2008-1815. Epub 2009 Nov 11.

  PMID: 19906788 BACKGROUND

• Sacher J, Mossaheb N, Spindelegger C, Klein N, Geiss-Granadia T, Sauermann R, Lackner E, Joukhadar C, Muller M, Kasper S. Effects of olanzapine and ziprasidone on glucose tolerance in healthy volunteers. Neuropsychopharmacology. 2008 Jun;33(7):1633-41. doi: 10.1038/sj.npp.1301541. Epub 2007 Aug 22.

  PMID: 17712347 BACKGROUND

• Vidarsdottir S, Vlug P, Roelfsema F, Frolich M, Pijl H. Orally disintegrating and oral standard olanzapine tablets similarly elevate the homeostasis model assessment of insulin resistance index and plasma triglyceride levels in 12 healthy men: a randomized crossover study. J Clin Psychiatry. 2010 Sep;71(9):1205-11. doi: 10.4088/JCP.08m04654yel. Epub 2010 Apr 20.

  PMID: 20441717 BACKGROUND

• Fountaine RJ, Taylor AE, Mancuso JP, Greenway FL, Byerley LO, Smith SR, Most MM, Fryburg DA. Increased food intake and energy expenditure following administration of olanzapine to healthy men. Obesity (Silver Spring). 2010 Aug;18(8):1646-51. doi: 10.1038/oby.2010.6. Epub 2010 Feb 4.

  PMID: 20134408 BACKGROUND

MeSH Terms

Interventions

Olanzapine

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Dost Öngür
• Organization: McLean Hospital

dongur@partners.org

617-855-3922

Study Officials

• Dost Ongur, MD, PhD

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief of Psychotic Disorders Division at McLean Hospital and Associate Professor in Psychiatry at Harvard Medical School

Study Record Dates

• First Submitted: August 20, 2015
• First Posted: September 1, 2015
• Study Start: November 17, 2017
• Primary Completion: November 8, 2019
• Study Completion: November 8, 2019
• Last Updated: October 3, 2022
• Results First Posted: August 12, 2021

Record last verified: 2022-09

Locations

US (1)