Validation & Intervention Testing for Aging, Longevity and Healthspan (VITAL-H)

Validation & Intervention Testing for Aging, Longevity and Healthspan (VITAL-H)

The study aims to address the gap between lifespan and healthspan (years of life free of age-related diseases and disabilities) by testing whether 2 approved U.S Food and Drug Administration (FDA) medications, dapagliflozin and semaglutide, can help people stay healthier as they age and delay the age-related functional decline. The study will test these medications over 36 months of treatment plus 6 months of observational follow up to see if they can safely maintain health and function during aging and eventually support their use for extending healthspan.

This study is being done because there are limited ways to slow down the age-related health and functional decline, and few reliable ways to measure early changes in healthspan in humans. The 2 study drugs have shown promising results in laboratory and early human studies, but more evidence is needed.

Study Overview

• Status: Not yet recruiting
• Conditions: Aging; Functional Decline
• Intervention / Treatment: Drug: Semaglutide oral; Other: Placebo; Drug: Dapagliflozin 10Mg Oral Tablet

Detailed Description

Phase 2b, hybrid-decentralized, double-blind, randomized placebo-controlled trial to evaluate the independent effects of dapagliflozin, oral semaglutide, and placebo on functional decline in healthy adults aged 60-75 years. 1200 individuals will be randomized to parallel intervention arms and followed for 36 months of intervention plus 6 months post-intervention follow-up to evaluate changes in locomotion (continuous short physical performance battery - primary outcome), vitality (peak oxygen uptake during exercise, VO2 peak - secondary outcome). Exploratory outcomes will include changes in body composition, individual components of intrinsic capacity (IC) across multiple functional geroscience-based domains, and overall intrinsic capacity. This hybrid-decentralized clinical trial integrates wearable technology, deep phenotyping, and biomarker analyses to evaluate if the proposed therapies demonstrate meaningful differences in functional healthy longevity outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 1200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Elena Volpi, MD, PhD; Phone Number: (210) 562- 6139; Email: volpi@uthscsa.edu
• Study Contact Backup: Name: Eloisa Martinez; Phone Number: 210-562-5078; Email: martineze42@uthscsa.edu

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Veterans Health Care System
      • Contact: Dean L Jr. Kellogg, MD, PhD; Phone Number: 210 617 5311; Email: KelloggD@uthscsa.edu
    • San Antonio, Texas, United States, 78207
      • Texas Diabetes Institute
      • Contact: Renata Belfort De Aguiar, MD, PhD; Phone Number: 210 -358 -7229; Email: belfortda@uthscsa.edu
    • San Antonio, Texas, United States, 78229
      • Sam and Ann Barshop Institute for Longevity & Aging Studies
      • Contact: Tiffany Cortes, MD; Phone Number: 210 450 8998; Email: cortest@uthscsa.edu
    • San Antonio, Texas, United States, 78227
      • San Antonio Food Bank
      • Contact: Shreya Rao, MD; Phone Number: 210 567 4600; Email: raos4@uthscsa.edu
    • San Antonio, Texas, United States, 78229
      • Barshop Institute Mobile Research Clinic
      • Contact: Shreya Rao, MD; Phone Number: 210 567 4600; Email: raos4@uthscsa.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ability to understand and the willingness to sign a written informed consent document.
2. Males and females; Age 60-75
3. Willingness to adhere to the study intervention regimen (dapagliflozin or semaglutide).
4. Body mass index 20-40 kg/m2
5. Community dwelling

Exclusion Criteria:

1. Any medical condition that, in the opinion of the investigator, would place the participant at increased risk for participation.

2. Participation in another treatment or intervention study within 6 months

3. Use of the following medication or supplements

   • That may be used for weight or appetite control
   • That may be used for glucose lowering
   • Immunosuppressant or biologics

4. Any of the following conditions

   • Myocardial infarction (MI), cerebrovascular accident (CVA/stroke), congestive heart failure (CHF) or revascularization procedures like percutaneous coronary intervention (stents)
   • Renal impairment with estimated glomerular filtration rate (eGFR<45)
   • Requirement of assistive devices for ambulation
   • Pancreatitis history (if cause has been removed then okay to enroll)
   • Recurrent urinary tract infections (2 or more within 6 months, or 3 or more within past 12 months)
   • Personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2
   • Active cancer (okay if in remission for ≥ 3 years or had non melanoma skin cancer)
   • Uncontrolled Hypertension above 160/90 (we will include individuals with controlled hypertension and no complications)
   • Diabetes or Hemoglobin A1c ≥6.5%
   • Multiple sclerosis, MS, Parkinson Disease, mild cognitive impairment, dementia
   • History of solid organ transplant

5. Planned elective orthopedic surgery during the study

6. Hypersensitivity to any of the study drugs

7. Prisoner

8. Females who are pregnant, breastfeeding, or planning to become pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide Arm; Semaglutide and dapagliflozin placebo are administered	Drug: Semaglutide oral; Participants will start taking a 1.5 mg semaglutide pill, titrated to 4 mg as tolerated, plus one placebo pill per day for 36 months.; Other Names: Weygovy pill; Other: Placebo; Participants will take two placebo pills daily for 36 months; Other Names: Inert tablet
Experimental: Dapagliflozin Arm; Dapagliflozin and semaglutide placebo are administered	Other: Placebo; Participants will take two placebo pills daily for 36 months; Other Names: Inert tablet; Drug: Dapagliflozin 10Mg Oral Tablet; Participants will take one dapagliflozin plus one placebo pill daily for 36 months; Other Names: Farxiga 10 mg
Placebo Comparator: Placebo Arm; The placebo arm consists of 2 placebos, one matched to each study drug with the same ingredients for both.	Other: Placebo; Participants will take two placebo pills daily for 36 months; Other Names: Inert tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Continuous Short Physical Performance Battery SPPB	This is a well-established objective measure of physical function that assesses standing balance, gait speed test, and repeated chair stands. The SPPB score ranges from 0 to 12, with higher scores indicating better lower extremity physical function.	Baseline to end of study (approximately 36 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physiological reserve	Measured as Cardio-Pulmonary Exercise Test (CPET) on a cycle ergometer to measure maximum oxygen consumption rate (VO2 peak) during exercise during a treadmill test on a stationary bicycle.	Baseline to end of study (approximately 36 months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-minute Walk Test	Distance walked at self-selected normal pace over 6 minutes	Baseline to end of study (approximately 36 months)
Grip strength	Isometric hand grip strength during a 3-5 second period	Baseline to end of study (approximately 36 months)
Montreal Cognitive Assessment (MOCA)	Participants will complete the MOCA a brief cognitive screening tool used to assess cognitive function on person or remotely, as applicable. Scores are calculated according to the standardized scoring procedures for the version administered, with higher scores indicating better cognitive function.	Baseline to end of study (approximately 36 months)
Center for Epidemiological Studies Depression Scale (CES-D)	Total scores range from 0 to 60, with higher scores indicating greater depressive symptom burden.	Baseline to end of study (approximately 36 months)
Glycosolated hemoglobin (HbA1c)	Percentage of glucose in hemoglobin averaged over a 3 month period	Baseline to end of study (approximately 36 months)
Body weight	Body weight (kg)	Baseline to end of study (approximately 36 months)
Body mass index (BMI)	Body mass index is calculated using weight (kg) and height (meters)	Baseline to 36 weeks
Visual acuity	Measured using Snellen test	Baseline to end of study (approximately 36 months)
Hearing thresholds (dB)	Hearing is tested using a hand-held portable audiometer at various frequencies.	Baseline to end of study (approximately 36 months)
Pulmonary Function (FEV1)	Measure of peak expiratory flow (FEV1) using a portable spirometer.	Baseline to 36 months
Fat free mass	Measured by Bioelectrical Impedance Analysis (BIA)	Baseline to end of study (approximately 36 months)
Body fat percentage	Measured by Bioelectrical Impedance Analysis (BIA)	Baseline to end of study (approximately 36 months)
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)	calculated from fasting insulin and fasting glucose	Baseline to end of study (approximately 36 months)
Nutritional Status	Mini Nutritional Assessment (MNA) is a 6-item screening tool with total scores ranging from 0 to 14. Scores of 12-14 indicate normal nutritional status, 8-11 indicate risk of malnutrition, and 0-7 indicate malnourished.	Baseline to end of study (approximately 36 months)

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: Department of Health and Human Services

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): February 1, 2031

Study Registration Dates

• First Submitted: October 26, 2026
• First Submitted That Met QC Criteria: November 3, 2026
• First Posted (Actual): November 6, 2026

Study Record Updates

• Last Update Posted (Actual): November 6, 2026
• Last Update Submitted That Met QC Criteria: November 3, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Keywords: Healthspan; Lifespan; Community dwelling
• Additional Relevant MeSH Terms: Pharmaceutical Preparations; Dosage Forms; semaglutide; Tablets; dapagliflozin
• Other Study ID Numbers: STUDY00002818; ARPA-H/1AY2AX000159 - 01 (Other Grant/Funding Number: DHHS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Only deidentified individual participant data (IPD) will be shared with the entitites involved at sites used for the study and possibly the data safety monitoring board if needed. Any public data will be shared as aggregated data on ClinicalTrials.gov or in a peer review journal.

IPD Sharing Time Frame

After study completion and when data are analyzed

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No