Intranasal Oxytocin Intervention for Caregivers to Persons With Dementia

Overview

More than 15 million family caregivers provide support for individuals with Alzheimer's disease (AD) or related dementias. This number is expected to grow with the increasing population of persons with dementia (PWD). Stress in caregivers to older adults with chronic diseases is already a significant public health issue because it is associated with multiple negative physical and mental health outcomes for the caregiver (e.g., depression, cardiovascular disease) and can negatively impact the health of the PWD as well. Importantly, stress levels are even higher in female than male caregivers and in caregivers to PWD than other chronic conditions that affect older adults. There are numerous interventions to improve well-being in caregivers to PWD, but only two have been shown to moderately improve caregiver depression and quality of life in the PWD. However, both of the interventions are time and energy intensive. One promising candidate to reduce stress and improve quality of life is the endogenous neuropeptide oxytocin (OXT). Intranasal OXT interventions have been shown to successfully reduce stress and increase quality of life in other populations, including patients with borderline personality disorder, Post-traumatic Stress Disorder (PTSD), Anxiety Disorder, and Depressive Disorder. This study will assess the efficacy and safety of intranasal oxytocin (OXT) to improve the quality of life and reduce chronic stress levels in the caregivers to PWD. Participants will be randomly enrolled to one of three groups: 12 IU intranasal oxytocin, 24 IU intranasal oxytocin or placebo. The study drug will be administered daily for 21 days.

Detailed description

More than 15 million family caregivers provide support for individuals with Alzheimer's disease (AD) or related dementias. This number is expected to grow with the increasing population of persons with dementia (PWD). Stress in caregivers to older adults with chronic diseases is already a significant public health issue because it is associated with multiple negative physical and mental health outcomes for the caregiver (e.g., depression, cardiovascular disease) and can negatively impact the health of the PWD as well. Importantly, stress levels are even higher in female than male caregivers and in caregivers to a PWD than other chronic conditions that affect older adults. One promising candidate to reduce stress and improve quality of life is the endogenous neuropeptide oxytocin (OXT). Intranasal OXT interventions have been shown to successfully reduce stress and increase quality of life in other populations, including patients with borderline personality disorder, Post-traumatic Stress Disorder (PTSD), Anxiety Disorder, and Depressive Disorder. 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.

Eligible females who are family caregivers to a PWD for a least five hours a week for six consecutive months will be randomly enrolled to one of three groups: 12 IU intranasal oxytocin, 24 IU intranasal oxytocin or placebo. The study drug will be administered daily for 21 days. Surveys and questionnaires that evaluate mental and emotional health and functional magnetic resonance imaging (fMRI) will be administered before and after the study treatment to see if oxytocin will help improve quality of life better and lower stress levels in caregivers to people who have dementia. Additionally, the study will find out if the brain responds to oxytocin.

Interventions

• Drug Placebo
  Placebo intranasal spray liquid with no oxytocin will be delivered in 2 puffs to each nostril daily for 21 days. The first single dose will be administered at the clinic (Visit 1).
• Drug Oxytocin Intranasal Spray 12 International Unit (12IU)
  Participants weighing less than 40 kg (88 pounds) 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).
• Drug Oxytocin Intranasal Spray 24 International Unit (24IU)
  Participants weighing more than 40 kg (880 pounds) 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 Empathy and Theory of Mind task (EmpaTom task will administered pre- and post-administration of oxytocin.

Primary outcome measures

• Chronic Stress Level in the Past Thirty Days [Time frame: Baseline (Visit 1) and Post-intervention (Visit 2)]

Secondary outcome measures (2)

• Participant Quality of Life [Time frame: Baseline (Visit 1) and Post-intervention (Visit 2)]
• Blood Oxygen Level Dependent (BOLD) responses in neural areas during the Affective Stroop task (AS) and Empathy and Theory of Mind(EmpaToM) task [Time frame: Baseline (Visit 1) and Post-intervention (Visit 2) It will take about 60 minutes to complete at each time point.]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Basic science

Study locations

United States · 1 center

• University of Nebraska Medical Center, Department of Psychiatry — Omaha

Publications

• Alzheimers Association. 2015 Alzheimers Disease Facts and Figures. (2015).
• 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. PMID 12825775
• 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. PMID 34986661
• 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. PMID 32816014
• 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. PMID 31515084
• 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: 10.1080/0895 PMID 35343403
• 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. PMID 30452088
• 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 PMID 34486887

Identifiers

NCT: NCT06364228 · 0133-24-FB

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗