- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04344873
Impact of T Cells on Age-related Vascular Dysfunction: A Translational Approach
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Advanced age is the primary and most predictive risk factor for CVD. The investigators have demonstrated that there is a pronounced age-associated increase in T cell infiltration into the perivascular space around large elastic arteries and small resistance arteries. The objective of this study is to determine if and how T cells contribute to age-related arterial inflammation and dysfunction.
Although there is evidence from rodent studies that T cells play a critical role in arterial dysfunction, it is unknown whether this occurs in humans. Abatacept, a T cell co-stimulation inhibitor, is FDA approved for treatment of rheumatoid arthritis. Importantly, Abatacept decreases the inflammatory phenotype of circulating T cells. Abatacept will be used in older adults to be the first to determine if T cell inflammation contributes to arterial dysfunction in older adults. The investigators hypothesize that older adults treated with Abatacept will exhibit greater flow-mediated dilation, decreased pulse wave velocity, decreased or unchanged blood pressure, decreased inflammatory and oxidative stress markers in endothelial cells, decreased plasma free radicals, decreased proportion of memory T cells, and experience a shift away from a pro-inflammatory T cell phenotype compared to placebo. These results will be interpreted to mean that T cells play a role in mediating age-related arterial dysfunction in humans.
Study Type
Enrollment (Estimated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: Anthony Donato
- Phone Number: 801-584-2522
- Email: tony.donato@hsc.utah.edu
Study Contact Backup
- Name: Adelola Adeyemo
- Phone Number: 801-582-1565
- Email: lola.adeyemo@utah.edu
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Older adults (55-75 years old).
- Women will be at least two years postmenopausal, not using hormone therapy and have a follicle stimulating hormone (FSH) concentration of >30 IU/L.
Exclusion Criteria:
- Autoimmune disorders,
- Hypertension (blood pressure >140/90mmHg),
- Body mass index of >30 kg/m2,
- Clinical CVD,
- Diabetes
- Current tobacco use,
- Regular aerobic exercise (>30 mins per day, > 2 days per week for the at least the last 2 years),
- Current or recurring infections within 12 weeks of the baseline visit,
- A positive tuberculosis (TB) test or subjects at risk of TB,
- Positive test for Hepatitis B, C, or cytomegalovirus (CMV),
- Use of immunosuppressive medication,
- Vaccination within 4 weeks of the baseline visit,
- Major surgery within 8 weeks of the baseline visit,
- Previous lymphoid irradiation or bone marrow transplant,
- Subjects at risk for diverticulitis,
- Any laboratory test result that, in the opinion of the overseeing physician (Dr. Frech) might place a participant at unacceptable risk.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Older Adult participants
Older adult participants (ages 55-75) will be assessed for arterial function using FMD analysis, PWV calculations, T Cell phenotyping, and proportion of inflammatory biomarkers after injections of placebo and abatacept.
|
Placebo injection at day one and day fourteen.
Abatacept injection at day twenty eight and day forty two.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in brachial arterial diameter after abatacept injection.
Time Frame: 7 weeks
|
7 weeks
|
Change in brachial arterial flow rate after abatacept injection.
Time Frame: 7 weeks
|
7 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in pulse wave velocity as measured by doppler ultrasound after abatacept injection.
Time Frame: 7 weeks
|
7 weeks
|
Change in proportion of memory T-Cells after abatacept injection
Time Frame: 7 weeks
|
7 weeks
|
Change in proportion of inflammatory biomarker Tumour Necrosis Factor alpha (TNF-α) after abatacept injection
Time Frame: 7 weeks
|
7 weeks
|
Change in proportion of inflammatory biomarker Interferon gamma (IFN-γ) after abatacept injection
Time Frame: 7 weeks
|
7 weeks
|
Change in proportion of inflammatory biomarker interleukin 10 (IL-10) after abatacept injection
Time Frame: 7 weeks
|
7 weeks
|
Change in proportion of inflammatory biomarker interleukin 17 (IL-17) after abatacept injection
Time Frame: 7 weeks
|
7 weeks
|
Change in proportion of inflammatory biomarker forkhead box P3 (FoxP3) after abatacept injection
Time Frame: 7 weeks
|
7 weeks
|
Change in proportion of inflammatory biomarker perforin after abatacept injection
Time Frame: 7 weeks
|
7 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB_00118392
- R01AG060395 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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