Impact of T Cells on Age-related Vascular Dysfunction: A Translational Approach

NCT04344873 | Withdrawn Early Phase 1 DMC FDA Drug

• 2 other identifiers: IRB_00118392R01AG060395
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States and other industrialized societies, and advanced age is the major risk factor for development of CVD. Advancing age appears to exert its pathological influence primarily via adverse functional and structural effects on arteries. Aging is associated with increased stiffness (reduced compliance) of large elastic arteries and impaired arterial endothelial function that is characterized by reductions in nitric oxide (NO)- mediated endothelium-dependent dilation (EDD). While several changes to arteries may contribute to age-associated increases in CVD risk; the development of endothelial dysfunction and stiffening of the large elastic arteries are among the most important contributors. Both are predictors of CV events and clinical CVD with increasing age. Although the importance of endothelial dysfunction and arterial stiffening with age are well established, the initiating events of these deleterious changes are elusive.

Conditions

Inflammation; Aging; Cardiovascular Diseases

Keywords

Aging; Inflammation; Cardiovascular disease

Outcome Measures

Primary Outcomes (2)

• Change in brachial arterial diameter after abatacept injection.

  7 weeks

• Change in brachial arterial flow rate after abatacept injection.

  7 weeks

Secondary Outcomes (8)

• Change in pulse wave velocity as measured by doppler ultrasound after abatacept injection.

  7 weeks

• Change in proportion of memory T-Cells after abatacept injection

  7 weeks

• Change in proportion of inflammatory biomarker Tumour Necrosis Factor alpha (TNF-α) after abatacept injection

  7 weeks

• Change in proportion of inflammatory biomarker Interferon gamma (IFN-γ) after abatacept injection

  7 weeks

• Change in proportion of inflammatory biomarker interleukin 10 (IL-10) after abatacept injection

  7 weeks

Study Arms (1)

Older Adult participants

EXPERIMENTAL

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.

Other: Placebo; Drug: Abatacept 10 mg/kg

Interventions

Placebo OTHER

Placebo injection at day one and day fourteen.

Older Adult participants

Abatacept 10 mg/kg DRUG

Abatacept injection at day twenty eight and day forty two.

Older Adult participants

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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,

Sponsors & Collaborators

• University of Utah: lead
• National Institute on Aging (NIA): collaborator

MeSH Terms

Conditions

Cardiovascular Diseases; Inflammation

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Geriatrics

Model Details: Prospective placebo controlled crossover design

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: April 14, 2020
• Study Start: September 1, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: January 12, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share