Acetate and Age-associated Arterial Dysfunction

NCT05424263 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-0473
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

Cardiovascular diseases are the leading cause of morbidity and mortality and contribute most to healthcare costs in the U.S. Age is the strongest cardiovascular disease risk factor, with \>90% of all deaths from cardiovascular disease occurring in adults \>50 years old. The age-associated increased risk of cardiovascular disease is due, in large part, to the development of arterial dysfunction, including endothelial dysfunction and stiffening of the large elastic arteries. Therefore, novel, effective interventions that improve arterial function will have a large public health impact by decreasing the risk of cardiovascular diseases. The short-chain fatty acid acetate is endogenously produced by the gut microbiome from fermentation of dietary soluble fiber. High-fiber diets reduce risk of cardiovascular diseases, but unfortunately, a low percentage of Americans meet guidelines for adequate dietary fiber intake and, despite nationwide efforts to improve this, trends in fiber intake have not improved over the last 20+ years. Thus, directly supplementing acetate may be a more practical and feasible intervention for effectively improving arterial function in older adults and reducing the risk of cardiovascular diseases. The investigators will conduct a study to determine the efficacy of 12 weeks of oral supplementation with acetate for improving arterial function in late middle-aged and older (50+ years) adults. They will also assess the safety and tolerability of acetate supplementation in these adults and perform innovative mechanistic analyses to determine how acetate supplementation improves arterial function. The investigators hypothesize that oral acetate supplementation will improve arterial function by decreasing oxidative stress and increasing nitric oxide bioavailability, and also hypothesize that acetate supplementation will be safe and promote high rates of adherence.

Conditions

Aging; Vascular Stiffness; Vascular Dilation

Keywords

Acetate; Short-chain fatty acids; Gut microbiome; Arterial function

Outcome Measures

Primary Outcomes (1)

• Change in Brachial Artery Flow-Mediated Dilation

  Nitric oxide-mediated endothelium dependent dilation (vascular endothelial function) will be assessed at baseline and end-intervention by flow-mediated dilation of the brachial artery determined using high-resolution ultrasonography (Canon Xario 200) and analyzed with a commercially available software package (Vascular Analysis Tools, Medical Imaging Applications, LLC). Brachial artery flow-mediated dilation will be assessed by measuring brachial artery diameter and forearm blood flow at baseline and for 2 minutes following reactive hyperemia induced by 5 minutes of forearm blood flow occlusion (upper forearm cuff placement). Data will be expressed as a percent change in arterial diameter from pre-cuff inflation diameter, and then as a change in this % from baseline to end-intervention.

  12 weeks

Secondary Outcomes (2)

• Change in Carotid-Femoral Pulse Wave Velocity (CFPWV)

  12 weeks

• Change in Casual (seated, resting) systolic blood pressure

  12 weeks

Other Outcomes (7)

• Change in 24-hour ambulatory blood pressure

  12 weeks

• Incidence of enrolled subjects dropping out of the study due to adverse events

  12 weeks

• % of prescribed amount of drug that is consumed

  12 weeks

Study Arms (2)

Acetate

EXPERIMENTAL

Subjects will be orally supplemented with calcium acetate for 12 weeks. Subjects will be instructed to take a volume of the oral liquid solution that contains 1,334 mg of calcium acetate 3x per day with meals, for a total dose of 4,000 mg/day. Calcium acetate will be compounded by the CU Anschutz Medical Campus Research Pharmacy and dispensed to subjects in 4-week supplies.

Drug: Calcium Acetate Oral Solution

Placebo

PLACEBO COMPARATOR

Subjects will be orally supplemented with calcium carbonate for 12 weeks. This placebo has been selected to match any potential effects of calcium and phosphate binding of the calcium acetate, i.e., we will isolate the effects of acetate. Subjects will be instructed to take a volume of the oral liquid solution equal to that of the calcium acetate group 3x per day with meals. To match the amount of elemental calcium between calcium acetate and calcium carbonate, this dose of calcium carbonate will contain 833 mg of calcium carbonate, for a total dose of 2,500 mg/day. Calcium carbonate will be compounded by the CU Anschutz Medical Campus Research Pharmacy, visually identical to calcium acetate including the packaging, and dispensed to subjects in 4-week supplies.

Drug: Calcium Carbonate Oral Suspension

Interventions

Calcium Acetate Oral Solution DRUG

Subjects will be supplemented with calcium acetate (4,000 mg/day), as described in the arm/group descriptions, for 12 weeks.

Also known as: Calcium acetate

Acetate

Calcium Carbonate Oral Suspension DRUG

Subjects will be supplemented with calcium carbonate (2,500 mg/day), as described in the arm/group descriptions, for 12 weeks.

Also known as: Calcium carbonate

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide informed consent;
• Age 50+ years;
• Serum phosphorus levels \>= 2.5 mg/dl at screening;
• Habitual dietary fiber intake \<30 g/day for men or \<21 g/day for women, based on Block Fiber Screener conducted at screening;
• Weight-stable in the 3 months prior to enrollment (self-report);
• Willing to abstain from dietary supplements for 48 hours and from alcohol, tobacco, and cannabis products for 24 hours before all visits;

You may not qualify if:

• History of current serious, chronic clinical disease, e.g., cardiovascular disease, diabetes, liver disease, Alzheimer's disease and related dementias, cancer;
• Major changes in health in the past 3 months, e.g., hospitalizations, major surgeries, significant changes in medications;
• Currently taking calcium acetate or any other calcium supplementation;
• Screening FMDba \> 8%;
• Body mass index \> 40 kg/m\^2 at screening;
• Regular vigorous/aerobic endurance \>4 bouts/week for \>30 min/bout at a workload of \>6 METS;
• Any apparent dependence on or abuse of alcohol, tobacco, and cannabis products;
• Pregnancy, breast-feeding, or plans to become pregnant during the duration of the study;
• Any finding on the medical history, physical exam, or standard clinical blood labs that, in the opinion of the physician of record, would put the subject at increased risk with calcium supplementation.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

MeSH Terms

Interventions

calcium acetate; Calcium Carbonate

Intervention Hierarchy (Ancestors)

Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals

Study Officials

• Vienna Brunt, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jill Herch, BS

CONTACT

303-724-5839; jill.herch@cuanschutz.edu

Vienna Brunt, PhD

CONTACT

303-724-4898; vienna.brunt@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study is double-blind. The study drug and placebo will be compounded into visually-identical oral liquid solutions and packaged in identical opaque brown medicine bottles. Only the pharmacy and biostatistician conducting the randomization will know which group subjects are assigned to.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2022
• First Posted: June 21, 2022
• Study Start: September 29, 2022
• Primary Completion: July 1, 2025
• Study Completion: September 1, 2025
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)