Intranasal Oxytocin Intervention for Caregivers to Persons With Dementia

Stress Clinical Trial

Official title:

Intranasal Oxytocin Intervention for Caregivers to Persons With Dementia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06364228
• Other study ID #: 0133-24-FB
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2024
• Est. completion date: April 2026

Study information

• Verified date: June 2024
• Source: University of Nebraska
• Contact: Soonjo Hwang, MD
• Phone: 402-552-6351
• Email: soonjo.hwang[@]unmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The proposed study is a double-blind, randomized, placebo-controlled study of intranasal oxytocin (OXT) to determine its efficacy in improving quality of life and reducing stress in caregivers to persons with dementia. Planned enrollment is 32 participants over 2 years.

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.

The current 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 32
• Est. completion date: April 2026
• Est. primary completion date: April 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 50 Years and older

Eligibility

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 in English

Exclusion Criteria:

• Major medical illness that contraindicates oxytocin (OXT) administration (e.g., severe liver disease, seizure disorder, metabolic disorder)

• Past 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 in the next few weeks 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 our 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.

Related Conditions & MeSH terms

• Dementia
• Stress

Intervention

Drug:
• Placebo
Placebo intranasal spray liquid administration. Oxytocin delivered 2 puffs to each nostril daily for 21 days. The first single dose will be administered at the clinic (visit 1).
• Oxytocin Intranasal Spray 12 International Unit (12IU)
Oxytocin intranasal spray liquid administration. Subjects weighing < 40 kg will receive 12 IU of oxytocin delivered as 1 puff (6 IU) to each nostril daily for 21 days. The first single dose will be administered at the clinic (visit 1).
• Oxytocin Intranasal Spray 24 International Unit (24IU)
Oxytocin intranasal spray liquid administration. Subjects weighing > 40 kg will receive 24 IU of oxytocin delivered as 2 puffs (12 IU) to each nostril daily for 21 days. The first single dose will be administered at the clinic (visit 1).

Procedure:
• Functional MRI
Functional MRI (fMRI) scan with affective Stroop and EmpaTom task (Empathy and Theory of Mind task). fMRI scan will administered pre and post-administration of oxytocin.

Locations

Country	Name	City	State
United States	University of Nebraska Medical Center, Department of Psychiatry	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
University of Nebraska

Country where clinical trial is conducted

United States, 

References & Publications (36)

Alzheimers Association. 2015 Alzheimers Disease Facts and Figures. (2015).

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. — View 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. — View 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. — View 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. — View 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.

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Lang PJ BM, Cuthbert BN. International affective picture system (IAPS): Affetive ratings of pictures and instruction manual. Gainesville, FL: University of Florida; 2005.

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. — View 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. — View 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. — View 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. Erratum In: Am J Psychiatry. 2008 Jul;165(7):920. Am J Psychiatry. 2008 May;165(5):652. — View 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. — View 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/ — View 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. — View 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. — View 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. — View 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.

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. — View 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. Erratum In: Gerontologist. 2021 Jul 13;61(5):804. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 36 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cognitive Orientation Screening	Participants will complete a brief cognitive orientation screening tool, called the Mini-Mental Status Exam. This will be administered by the research assistant. If the participant scores below 26 on this measure, they will be excluded from the study, as it may indicate potential cognitive issues. The scale ranges from 0 to 30, with higher scores indicating better cognitive performance (better outcomes).	Visit 1 (Baseline visit). Will take about 10 minutes.
Other	Geriatric Anxiety Scale (GAS-10)	10 Item Version (GAS-10). The rating scale ranges from 0 to 30 points. Higher scores indicate more severe anxiety (worse outcomes).	Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 5 minutes to complete at each time point.
Other	Geriatric Depression Scale Short Form (GDS-SF)	The rating scale is from 0 to 15 points. Higher scores indicate more likelihood of depression symptoms and need for further assessment of depression (worse outcomes).	Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 7 minutes to complete at each time point.
Other	Alcohol Use Disorders Identification Test (AUDIT Alcohol Screening Tool)	Scores can range from 0 -40. Higher scores indicate a greater likelihood of harmful alcohol consumption (worse outcomes).	Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 10 minutes to complete at each time point.
Other	Neuropsychiatric Inventory-Questionnaire (NPI-Q)	Caregivers will be asked to complete NPI-Q. There are 12 domains and for each domain there is an item that indicates the specific symptoms of the domain. The caregiver indicates whether the symptom was present by selecting: "Yes" (present) or "No" (absent). If the caregiver selects "yes", they then rate the severity of the symptoms within the last month on a 3-point scale. They also rate the impact of the individual with dementia's symptoms on them personally (Distress) using a 5-point scale. There are Symptom Severity and Distress ratings for each of the listed symptoms. There are also total Severity and Distress scores which are the sum of the individual domain scores. The total score for Symptom Severity ranges from 0 to 36, with higher scores indicating more severe symptoms (worse outcomes). For the Distress Scale, the scores range from 0 to 60, with higher scores indicating more extreme levels of distress (worse outcomes).	Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 5 minutes to complete at each time point.
Other	Quick Dementia Rating Scale (QDRS)	Participants will be asked to complete the QDRS about the individual for whom they are providing care. The QDRS measures 10 different domains that focus on aspects of their daily functioning, mood, and behavior. For each domain, the caregiver is asked to rate the severity of the individual with dementia's symptoms. The scores on the QDRS range from 0-30, with higher scores indicating more impairment in the individual with dementia (worse outcomes).	Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 5 minutes to complete at each time point.
Other	The Interpersonal Reactivity Index (IRI)	The Interpersonal Reactivity Index (IRI) is a multidimensional measure of empathy. There are four empathy subscales which include the Perspective Taking, Empathic Concern, Personal Distress, and Fantasy subscales. Each subscale has 7 items, and specific items need to be reverse scored. Item responses range from 0 to 4. The range of values for each subscale is 0 to 28. Higher scores indicate greater empathy for that specific domain (better outcomes).	Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 10 minutes to complete at each time point.
Primary	Participants' chronic stress levels in the past thirty days.	Will be assessed by the Perceived Stress Scale total score. Scores can range from 0 to 40. Higher scores on this scale indicate higher levels of perceived stress (a worse outcome).	Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 5 minutes to complete at each time point.
Secondary	Participant Quality of Life survey	Will be assessed by the Health Organization Quality of Life- Short version (WHO-QOL-BREF) which measures general perceptions about quality of life as well as four aspects of life: physical health, psychological health, social relationships, and environment. The secondary outcome that will be measured will be the participant ratings of the specific item, "How would you rate your quality of life?" The rating for this item ranges from 1 ('very poor') to 5 ('very good'), with higher scores indicating a better outcome.	Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 15 minutes to complete at each time point.
Secondary	Blood Oxygen Level Dependent (BOLD) responses in neural areas during the Affective Stroop task (AS) and Empathy and Theory of Mind(EmpaToM) task.	Neural level changes as measured by Functional Magnetic Resonance Imaging (fMRI)	Visit 1 (Baseline visit) and Visit 2 (Post-intervention visit). It will take about 60 minutes to complete at each time point.