Clinical trial NCT06364228: Intranasal Oxytocin Intervention for Caregivers to Persons With Dementia
Official title: Intranasal Oxytocin Intervention for Caregivers to Persons With Dementia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Stress
Keywords: Oxytocin
Stress level
Caregivers
Dementia
fMRI
Neuroimaging
Quality of Life
Lead sponsor: University of Nebraska
Sponsor class: OTHER
First posted: 2024-04-15
Enrollment: 32
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The overall aim of this study is to determine the efficacy and safety of intranasal oxytocin (OXT) to improve the quality of life and reduce chronic stress levels in the caregivers to the persons with dementia. Randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin (12 or 24 IU) will be conducted by daily administration (once a day) for 21 days (3 weeks).

Detailed description: The overall aim of this study is to determine the efficacy and safety of intranasal oxytocin (OXT) to improve the quality of life and reduce chronic stress levels in the caregivers to the persons with dementia. Randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin (12 or 24 IU) will be conducted by daily administration (once a day) for 21 days (3 weeks).

Endogenous neuropeptide oxytocin (OXT) has been a focus of prior psychiatric research based upon its role in pro-social behavior and modulation of response to social/emotional stimuli. However, currently there is no comprehensive study examining its role in the caregivers to chronic medical/psychiatric illnesses including dementia for potential beneficial impact as well as reducing chronic stress levels.

This study aims to establish intranasal OXT's efficacy and safety for these clinical implications. Investigators will also apply methods (task related functional MRI) that have shown verifiable and measurable ability to capture the core target area (mPFC and amygdala) and its change in response to OXT.

This project will lead to progress in understanding the potential role of OXT on the relationship between caregiver and the person with chronic medical/psychiatric illnesses such as dementia. It will also guide future direction for clinical use of intranasal OXT for this critical population.

Eligibility criteria: Inclusion Criteria:

* Females 50 years of age or older
* Currently an unpaid family caregiver to an older adult (50 years and older) with dementia for at least five hours a week for at least six months
* Normal or corrected to normal vision and hearing
* Mobility to travel to University of Nebraska Medical Center (UNMC) for study procedures including brain imaging
* Right-handed
* Capacity to read and write English

Exclusion Criteria:

* Major medical illness that contraindicates oxytocin (OXT) administration (e.g., severe liver disease, seizure disorder, metabolic disorder)
* History of allergic reaction to oxytocin (OXT) and its nasal spray product
* History of central nervous system (CNS) disease, including history of seizure, epilepsy, CNS tumor, CNS hemorrhage, or serious CNS infection including meningitis or encephalitis
* Currently pregnant or planning to become pregnant during the course of the study
* Metal in the body (i.e., hearing aid, cardiac pacemaker, bone plates, braces, non-removable piercing/implants, etc.), claustrophobia, or any other condition that would preclude magnetic resonance imaging (MRI) scanning
* Mini-mental status exam score of 25 or lower which suggests possible cognitive issues
* History of or current neurological disease (e.g., stroke, traumatic brain injury, brain tumor, dementia)
* History of or current severe psychiatric disease (e.g., schizophrenia, bipolar disorder, autism, severe post-traumatic stress disorder)
* History of, or current drug or alcohol abuse
* Currently breastfeeding
* Current coronavirus disease-19 (COVID-19) illness
* Left-handed due to brain structural difference between right and left-handed individuals
* Currently taking antipsychotic medications, selective serotonin reuptake inhibitors (SSRIs) or corticosteroid creams/pills

Primary outcomes:
measure: Participant's Chronic Stress Levels in the Past Thirty Days
timeFrame: Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 5 minutes to complete at each time point.
Secondary outcomes:
measure: Participant Quality of Life survey
timeFrame: Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 15 minutes to complete at each time point.
measure: Blood Oxygen Level Dependent (BOLD) responses in neural areas during the Affective Stroop task (AS) and Empathy and Theory of Mind(EmpaToM) task
timeFrame: Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 60 minutes to complete at each time point.
Other outcomes:
measure: Cognitive Orientation Screening
timeFrame: Visit 1 (Baseline visit). It will take about 10 minutes.
measure: Geriatric Anxiety Scale (GAS-10)
timeFrame: Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 5 minutes to complete at each time point.
measure: Geriatric Depression Scale Short Form (GDS-SF)
timeFrame: Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 7 minutes to complete at each time point.
measure: Alcohol Use Disorders Identification Test (AUDIT Alcohol Screening Tool)
timeFrame: Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 10 minutes to complete at each time point.
measure: Neuropsychiatric Inventory-Questionnaire (NPI-Q)
timeFrame: Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 5 minutes to complete at each time point.
measure: Quick Dementia Rating Scale (QDRS)
timeFrame: Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 5 minutes to complete at each time point.
measure: The Interpersonal Reactivity Index (IRI)
timeFrame: Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 10 minutes to complete at each time point.
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center, Department of Psychiatry
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Soonjo Hwang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alzheimers Association. 2015 Alzheimers Disease Facts and Figures. (2015).
citation: Pinquart M, Sorensen S. Differences between caregivers and noncaregivers in psychological health and physical health: a meta-analysis. Psychol Aging. 2003 Jun;18(2):250-67. doi: 10.1037/0882-7974.18.2.250.
citation: Peavy G, Mayo AM, Avalos C, Rodriguez A, Shifflett B, Edland SD. Perceived Stress in Older Dementia Caregivers: Mediation by Loneliness and Depression. Am J Alzheimers Dis Other Demen. 2022 Jan-Dec;37:15333175211064756. doi: 10.1177/15333175211064756.
citation: Sheehan OC, Haley WE, Howard VJ, Huang J, Rhodes JD, Roth DL. Stress, Burden, and Well-Being in Dementia and Nondementia Caregivers: Insights From the Caregiving Transitions Study. Gerontologist. 2021 Jul 13;61(5):670-679. doi: 10.1093/geront/gnaa108.
citation: Bouchard K, Greenman PS, Pipe A, Johnson SM, Tulloch H. Reducing Caregiver Distress and Cardiovascular Risk: A Focus on Caregiver-Patient Relationship Quality. Can J Cardiol. 2019 Oct;35(10):1409-1411. doi: 10.1016/j.cjca.2019.05.007. Epub 2019 Sep 9.
citation: Losada-Baltar A, Vara-Garcia C, Pedroso-Chaparro MDS, Cabrera I, Jimenez-Gonzalo L, Fernandes-Pires J, Huertas-Domingo C, Barrera-Caballero S, Gallego-Alberto L, Romero-Moreno R, Marquez-Gonzalez M. Family caregivers of people with dementia in the context of the sociocultural stress and coping model: An examination of gender differences. J Women Aging. 2023 Jul-Aug;35(4):354-368. doi: 10.1080/08952841.2022.2052705. Epub 2022 Mar 26.
citation: Riffin C, Van Ness PH, Wolff JL, Fried T. Multifactorial Examination of Caregiver Burden in a National Sample of Family and Unpaid Caregivers. J Am Geriatr Soc. 2019 Feb;67(2):277-283. doi: 10.1111/jgs.15664. Epub 2018 Nov 19.
citation: Marques MJ, Tan EYL, Woods B, Jelley H, Kerpershoek L, Hopper L, Irving K, Bieber A, Stephan A, Skoldunger A, Sjolund BM, Selbaek G, Rosvik J, Zanetti O, Portolani DM, Maroco J, de Vugt M, Verhey F, Goncalves-Pereira M; Actifcare Consortium. Trajectories of relationship quality in dementia: a longitudinal study in eight European countries. Aging Ment Health. 2022 Nov;26(11):2307-2315. doi: 10.1080/13607863.2021.1969641. Epub 2021 Sep 6.
citation: National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Care Services; Board on Health Sciences Policy; Committee on Care Interventions for Individuals with Dementia and Their Caregivers; Stroud C, Larson EB, editors. Meeting the Challenge of Caring for Persons Living with Dementia and Their Care Partners and Caregivers: A Way Forward. Washington (DC): National Academies Press (US); 2021 Feb 23. Available from http://www.ncbi.nlm.nih.gov/books/NBK567818/
citation: Butler M, et al. Care Interventions for People Living With Dementia and Their Caregivers. Comparative Effectiveness Review No. 231. (Prepared by the Minnesota Evidence-based Practice Center under Contract No. 290-2015-00008-I.) AHRQ Publication No. 20-EHC023. Rockville, MD: Agency for Healthcare Research and Quality; August 2020. Errata December 2020. DOI: https://doi.org/10.23970/AHRQEPCCER231.
citation: Cochran DM, Fallon D, Hill M, Frazier JA. The role of oxytocin in psychiatric disorders: a review of biological and therapeutic research findings. Harv Rev Psychiatry. 2013 Sep-Oct;21(5):219-47. doi: 10.1097/HRP.0b013e3182a75b7d.
citation: Viero C, Shibuya I, Kitamura N, Verkhratsky A, Fujihara H, Katoh A, Ueta Y, Zingg HH, Chvatal A, Sykova E, Dayanithi G. REVIEW: Oxytocin: Crossing the bridge between basic science and pharmacotherapy. CNS Neurosci Ther. 2010 Oct;16(5):e138-56. doi: 10.1111/j.1755-5949.2010.00185.x. Epub 2010 Jul 7.
citation: Simeon D, Bartz J, Hamilton H, Crystal S, Braun A, Ketay S, Hollander E. Oxytocin administration attenuates stress reactivity in borderline personality disorder: a pilot study. Psychoneuroendocrinology. 2011 Oct;36(9):1418-21. doi: 10.1016/j.psyneuen.2011.03.013. Epub 2011 May 4.
citation: Olff M, Frijling JL, Kubzansky LD, Bradley B, Ellenbogen MA, Cardoso C, Bartz JA, Yee JR, van Zuiden M. The role of oxytocin in social bonding, stress regulation and mental health: an update on the moderating effects of context and interindividual differences. Psychoneuroendocrinology. 2013 Sep;38(9):1883-94. doi: 10.1016/j.psyneuen.2013.06.019. Epub 2013 Jul 12.
citation: De Cagna F, Fusar-Poli L, Damiani S, Rocchetti M, Giovanna G, Mori A, Politi P, Brondino N. The Role of Intranasal Oxytocin in Anxiety and Depressive Disorders: A Systematic Review of Randomized Controlled Trials. Clin Psychopharmacol Neurosci. 2019 Feb 28;17(1):1-11. doi: 10.9758/cpn.2019.17.1.1.
citation: Arueti M, Perach-Barzilay N, Tsoory MM, Berger B, Getter N, Shamay-Tsoory SG. When two become one: the role of oxytocin in interpersonal coordination and cooperation. J Cogn Neurosci. 2013 Sep;25(9):1418-27. doi: 10.1162/jocn_a_00400. Epub 2013 Apr 11.
citation: Levy J, Goldstein A, Zagoory-Sharon O, Weisman O, Schneiderman I, Eidelman-Rothman M, Feldman R. Oxytocin selectively modulates brain response to stimuli probing social synchrony. Neuroimage. 2016 Jan 1;124(Pt A):923-930. doi: 10.1016/j.neuroimage.2015.09.066. Epub 2015 Oct 9.
citation: Grace SA, Rossell SL, Heinrichs M, Kordsachia C, Labuschagne I. Oxytocin and brain activity in humans: A systematic review and coordinate-based meta-analysis of functional MRI studies. Psychoneuroendocrinology. 2018 Oct;96:6-24. doi: 10.1016/j.psyneuen.2018.05.031. Epub 2018 May 24.
citation: Kendrick KM, Guastella AJ, Becker B. Overview of Human Oxytocin Research. Curr Top Behav Neurosci. 2018;35:321-348. doi: 10.1007/7854_2017_19.
citation: Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. doi: 10.1016/0022-3956(75)90026-6. No abstract available.
citation: Mueller AE, Segal DL, Gavett B, Marty MA, Yochim B, June A, Coolidge FL. Geriatric Anxiety Scale: item response theory analysis, differential item functioning, and creation of a ten-item short form (GAS-10). Int Psychogeriatr. 2015 Jul;27(7):1099-111. doi: 10.1017/S1041610214000210. Epub 2014 Feb 27.
citation: Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982-1983;17(1):37-49. doi: 10.1016/0022-3956(82)90033-4.
citation: Weintraub S, Salmon D, Mercaldo N, Ferris S, Graff-Radford NR, Chui H, Cummings J, DeCarli C, Foster NL, Galasko D, Peskind E, Dietrich W, Beekly DL, Kukull WA, Morris JC. The Alzheimer's Disease Centers' Uniform Data Set (UDS): the neuropsychologic test battery. Alzheimer Dis Assoc Disord. 2009 Apr-Jun;23(2):91-101. doi: 10.1097/WAD.0b013e318191c7dd.
citation: Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983 Dec;24(4):385-96. No abstract available.
citation: Development of the World Health Organization WHOQOL-BREF quality of life assessment. The WHOQOL Group. Psychol Med. 1998 May;28(3):551-8. doi: 10.1017/s0033291798006667.
citation: Blair KS, Smith BW, Mitchell DG, Morton J, Vythilingam M, Pessoa L, Fridberg D, Zametkin A, Sturman D, Nelson EE, Drevets WC, Pine DS, Martin A, Blair RJ. Modulation of emotion by cognition and cognition by emotion. Neuroimage. 2007 Mar;35(1):430-40. doi: 10.1016/j.neuroimage.2006.11.048. Epub 2007 Jan 18.
citation: Blair KS, Geraci M, Smith BW, Hollon N, DeVido J, Otero M, Blair JR, Pine DS. Reduced dorsal anterior cingulate cortical activity during emotional regulation and top-down attentional control in generalized social phobia, generalized anxiety disorder, and comorbid generalized social phobia/generalized anxiety disorder. Biol Psychiatry. 2012 Sep 15;72(6):476-82. doi: 10.1016/j.biopsych.2012.04.013. Epub 2012 May 15.
citation: Lang PJ BM, Cuthbert BN. International affective picture system (IAPS): Affetive ratings of pictures and instruction manual. Gainesville, FL: University of Florida; 2005.
citation: Hwang S, Nolan ZT, White SF, Williams WC, Sinclair S, Blair RJ. Dual neurocircuitry dysfunctions in disruptive behavior disorders: emotional responding and response inhibition. Psychol Med. 2016 May;46(7):1485-96. doi: 10.1017/S0033291716000118. Epub 2016 Feb 15.
citation: Hwang S, White SF, Nolan ZT, Craig Williams W, Sinclair S, Blair RJ. Executive attention control and emotional responding in attention-deficit/hyperactivity disorder--A functional MRI study. Neuroimage Clin. 2015 Oct 9;9:545-54. doi: 10.1016/j.nicl.2015.10.005. eCollection 2015.
citation: Marsh AA, Finger EC, Mitchell DG, Reid ME, Sims C, Kosson DS, Towbin KE, Leibenluft E, Pine DS, Blair RJ. Reduced amygdala response to fearful expressions in children and adolescents with callous-unemotional traits and disruptive behavior disorders. Am J Psychiatry. 2008 Jun;165(6):712-20. doi: 10.1176/appi.ajp.2007.07071145. Epub 2008 Feb 15.
citation: White SF, Marsh AA, Fowler KA, Schechter JC, Adalio C, Pope K, Sinclair S, Pine DS, Blair RJ. Reduced amygdala response in youths with disruptive behavior disorders and psychopathic traits: decreased emotional response versus increased top-down attention to nonemotional features. Am J Psychiatry. 2012 Jul;169(7):750-8. doi: 10.1176/appi.ajp.2012.11081270.
citation: Kanske P, Bockler A, Trautwein FM, Singer T. Dissecting the social brain: Introducing the EmpaToM to reveal distinct neural networks and brain-behavior relations for empathy and Theory of Mind. Neuroimage. 2015 Nov 15;122:6-19. doi: 10.1016/j.neuroimage.2015.07.082. Epub 2015 Aug 5.
citation: Galvin JE. THE QUICK DEMENTIA RATING SYSTEM (QDRS): A RAPID DEMENTIA STAGING TOOL. Alzheimers Dement (Amst). 2015 Jun 1;1(2):249-259. doi: 10.1016/j.dadm.2015.03.003.
citation: Kaufer DI, Cummings JL, Ketchel P, Smith V, MacMillan A, Shelley T, Lopez OL, DeKosky ST. Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory. J Neuropsychiatry Clin Neurosci. 2000 Spring;12(2):233-9. doi: 10.1176/jnp.12.2.233.
citation: Posner, K., Brent, D., Lucas, C., Gould, M., Stanley, B., Brown, G., Fisher, P., Zelazny, J., Burke, A., Oquendo, M., Mann, J. (2008). Columbia Suicide Severity Rating Scale (CSSRS) Since Last Visit. The Research Foundation for Mental Hygiene, Inc.