Antiorbital Calcium in Chronic Conditions (AntiAFib)

Evaluating Changes in Quality of Life and Epigenetic Methylation From Antiorbital Ionic Calcium in Older Adults With Chronic Conditions

The purpose of this study is to determine the mechanistic effects of an ionic calcium supplement in adults with atrial fibrillation, osteoarthritis, and hypertension. The study aims to determine if ionic calcium supplementation affects quality of life, rate of biological aging, bone densitometry, and blood biomarkers of bone metabolism over a six month period compared to non-ionic calcium comparator supplement.

Study Overview

• Status: Withdrawn
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Dietary supplement: Ionic Calcium; Dietary supplement: Calcium Carbonate

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97201
      • Helfgott Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Adults 55-75 years of age
• Active diagnosis of one of the following conditions:
• Stage 1 Hypertension with Non-valvular Atrial Fibrillation (AF) - including paroxysmal, persistent, or long-standing persistent AF with typical electrocardiographic characteristics (i.e., absence of identifiable p-waves with irregularly irregular ventricular rate) without known complications, heart disease, or congenital heart defects (e.g., rapid ventricular rate, recent myocardial infarction, heart failure, stroke, cardiomyopathy, etc.), self-reported but previously diagnosed by a healthcare professional;
• Stage 1 Hypertension (systolic blood pressure of 130-139, diastolic blood pressure of 80-89), self-reported but previously diagnosed by a healthcare professional;
• or, Osteoarthritis, self-reported but previously diagnosed by a healthcare professional.
• If diagnosed with AF, a European Heart Rhythm Association (EHRA) score of 2b or greater (i.e. Normal daily activity not affected by symptoms related to AF, but patient troubled by symptoms).
• On a stable dose of all medications prior to study entry (i.e., consistent dose for a minimum of three months)
• Willing to be randomized to take daily ionized calcium as a dietary supplement or placebo over the 24-week study period
• On a stable dose of dietary supplements for at least one month prior to enrollment
• Willing to avoid initiation of new supplements and/or medications unless otherwise indicated by a healthcare professional
• Willing to have blood drawn on 6 occasions, and fast for 10-12 hours before blood draws, over the study period
• Willing to have desktop ultrasound of wrist done on 3 occasions.
• Able to communicate via email, complete computer-administered questionnaires, and to read and write in English.
• Must be able to provide written informed consent
• Non-smokers (including tobacco and cannabis products, combusted or vaporized)
• Approved to be eligible for study participation at the discretion of the Principal Investigators, after review of the Formal Eligibility Screen results.
• Willing to avoid taking dietary supplements containing the following ingredients for the 24 weeks of study involvement: additional supplemental calcium in any form, vitamin D, vitamin K, selenium, magnesium, or zinc.

Exclusion criteria:

• Individuals with a current or past diagnosis of permanent AF
• Individuals with any thyroid or parathyroid disorders, or current use of thyroid medication for any reason.
• Individuals with chronic kidney or liver disease, cancer, colorectal disease, and "other rare disorders".
• Individuals with a current diagnosis of Congestive Heart Failure (CHF).
• Individuals with a current or past diagnosis of Traumatic Brain Injury (TBI), thromboembolism, or Cerebrovascular Accident (CVA)/Stroke.
• Use of dihydropyridine or non-dihydropyridine calcium channel blockers for any reason
• If diagnosed with atrial fibrillation, not on a stable dose of anti-coagulant or anti-platelet prescription medications (i.e., consistent dose for a minimum of three months)
• Abnormalities in coagulation studies (e.g., INR ≤ 2 or ≥ 3.0) or hypercalcemia at the clinical screening visit.
• Blood pressure ≥ 140/90 mmHg at the clinical screening visit.
• Current involvement or within 14 days prior to screening of a significant diet or weight loss program (such as NutriSystem, Jenny Craig, Atkin's or other low-carb diet programs) or very low-calorie liquid diet programs (such as Optifast, Medifast, and/or HMR)
• Hospitalization (for any reason other than a scheduled medical procedure unrelated to atrial fibrillation, hypertension, or osteoarthritis) within 3 months prior to screening
• Cardiac surgery within 3 months prior to screening
• Malignancy within the last 5 years (with the exception of basal cell carcinoma, squamous cell carcinoma, and/or carcinoma in situ of the cervix)
• Are allergic to corn.
• Women who are lactating, pregnant or planning pregnancy within the next six months
• Intake of ≥ 2 standardized alcohol-containing beverages per day, 14 per week, or ≥4 in any single day within the past 14 days.
• Women who experience menstrual periods, who are sexually active and are unwilling to use an appropriate form of contraception during the duration of the trial.
• Smoking tobacco or nicotine products (combusted or vaporized)
• Use of illicit drugs/substances (such as but not limited to cocaine, phencyclidine (PCP), and methamphetamine) within 14 days of screening
• Currently participating in another interventional research study, or participated in another interventional research study within 14 days of screening
• Do not have an active primary care provider or specialist (i.e., cardiologist, rheumatologist, orthopedist, etc.) managing their atrial fibrillation, hypertension, or osteoarthritis.
• Current use of: dietary supplements or medications utilized for chelation purposes (i.e., ethylenediaminetetraacetic acid; EDTA), or of chemotherapeutic agents.
• MoCA score of 16 or less upon screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ionic Calcium; Ionic calcium (IC) is a calcium in a free ionic state. Participants will be instructed to take 8mg of IC/60kg body weight dissolved into approximately 500ml of purified water. Participants will titrate their dose at the start of the study as follows: days 1-3: 1 dose per day 30 min prior to a meal; Days 4-6: twice per day, 30 minutes before meals; from day seven onward, the full dosage of three times per day, 30 minutes before meals.	Dietary supplement: Ionic Calcium; Ionic calcium (IC), a calcium in a free ionic state (i.e., non-protein bound), is purported to improve calcium uptake and homeostasis leading to improved cellular signaling that may have been disrupted through environmental and lifestyle stressors.
Active Comparator: Calcium Carbonate; Participants will be instructed to take 8mg of calcium carbonate/60kg body weight dissolved into approximately 500ml of purified water. Participants will titrate their dose at the start of the study as follows: days 1-3: 1 dose per day 30 min prior to a meal; Days 4-6: twice per day, 30 minutes before meals; from day seven onward, the full dosage of three times per day, 30 minutes before meals.	Dietary supplement: Calcium Carbonate; Calcium carbonate supplementation in a solution identical in appearance, consistency, and taste to the intervention supplement.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Biological Aging	Dunedin Pace of Aging Calculated objective measure of the rate of epigenetic aging	Baseline
Rate of Biological Aging	Dunedin Pace of Aging Calculated objective measure of the rate of epigenetic aging	Week 12
Rate of Biological Aging	Dunedin Pace of Aging Calculated objective measure of the rate of epigenetic aging	Week 24
Patient Reported Outcomes Measurement Information system-29 Physical Function Sub-domain	Quality of Life	Baseline
Patient Reported Outcomes Measurement Information system-29 Physical Function Sub-domain	Quality of Life	Week 2
Patient Reported Outcomes Measurement Information system-29 Physical Function Sub-domain	Quality of Life	Week 6
Patient Reported Outcomes Measurement Information system-29 Physical Function Sub-domain	Quality of Life	Week 12
Patient Reported Outcomes Measurement Information system-29 Physical Function Sub-domain	Quality of Life	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Systolic and Diastolic Blood Pressure	Objective measure of blood pressure	Baseline
Changes in Systolic and Diastolic Blood Pressure	Objective measure of blood pressure	Week 2
Changes in Systolic and Diastolic Blood Pressure	Objective measure of blood pressure	Week 6
Changes in Systolic and Diastolic Blood Pressure	Objective measure of blood pressure	Week 12
Changes in Systolic and Diastolic Blood Pressure	Objective measure of blood pressure	Week 24
Changes in Cognition	MoCA Assessment Score	Baseline
Changes in Cognition	MoCA Assessment Score	Week 6
Changes in Cognition	MoCA Assessment Score	Week 12
Changes in Cognition	MoCA Assessment Score	Week 24
Changes in Mood	Patient Health Questionnaire-9 Score	Baseline
Changes in Mood	Patient Health Questionnaire-9 Score	Week 2
Changes in Mood	Patient Health Questionnaire-9 Score	Week 6
Changes in Mood	Patient Health Questionnaire-9 Score	Week 12
Changes in Mood	Patient Health Questionnaire-9 Score	Week 24
Changes in Anxiety	Generalized Anxiety Disorder-7 Score	Baseline
Changes in Anxiety	Generalized Anxiety Disorder-7 Score	Week 2
Changes in Anxiety	Generalized Anxiety Disorder-7 Score	Week 6
Changes in Anxiety	Generalized Anxiety Disorder-7 Score	Week 12
Changes in Anxiety	Generalized Anxiety Disorder-7 Score	Week 24
Changes in Pain and Disability	Western Ontario and McMaster Universities Arthritis Index (WOMAC) Score	Baseline
Changes in Pain and Disability	Western Ontario and McMaster Universities Arthritis Index (WOMAC) Score	Week 2
Changes in Pain and Disability	Western Ontario and McMaster Universities Arthritis Index (WOMAC) Score	Week 6
Changes in Pain and Disability	Western Ontario and McMaster Universities Arthritis Index (WOMAC) Score	Week 12
Changes in Pain and Disability	Western Ontario and McMaster Universities Arthritis Index (WOMAC) Score	Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ultrasonometer Bone Densitometry	Bone density T score resulting from ultrasound	Week 12
Ultrasonometer Bone Densitometry	Bone density T score resulting from ultrasound	Week 24
Activated Partial Thromboplastin Time	Measure of blood coagulation	Week 2
Activated Partial Thromboplastin Time	Measure of blood coagulation	Week 6
Activated Partial Thromboplastin Time	Measure of blood coagulation	Week 12
Activated Partial Thromboplastin Time	Measure of blood coagulation	Week 24
Thrombin Time	Measure of blood coagulation	Week 12
Thrombin Time	Measure of blood coagulation	Week 24
Concentration of Serum Calcium (ionic)	Measure of non-protein bound calcium concentration in the serum	Week 12
Concentration of BUN (serum)	Measure of renal function and protein turnover	Week 2
Concentration of BUN (serum)	Measure of renal function and protein turnover	Week 6
Concentration of BUN (serum)	Measure of renal function and protein turnover	Week 12
Concentration of BUN (serum)	Measure of renal function and protein turnover	Week 24
Concentration of Creatinine (serum)	Measure of renal function	Week 2
Concentration of Creatinine (serum)	Measure of renal function	Week 6
Concentration of Creatinine (serum)	Measure of renal function	Week 12
Concentration of Creatinine (serum)	Measure of renal function	Week 24
Glomerular Filtration Rate, estimated (eGFR)	Measure of renal function	Week 2
Glomerular Filtration Rate, estimated (eGFR)	Measure of renal function	Week 6
Glomerular Filtration Rate, estimated (eGFR)	Measure of renal function	Week 12
Glomerular Filtration Rate, estimated (eGFR)	Measure of renal function	Week 24
Concentration of Alanine aminotransferase (serum)	Measure of liver function	Week 2
Concentration of Alanine aminotransferase (serum)	Measure of liver function	Week 6
Concentration of Alanine aminotransferase (serum)	Measure of liver function	Week 12
Concentration of Alanine aminotransferase (serum)	Measure of liver function	Week 24
Concentration of Aspartate aminotransferase (serum)	Measure of liver function	Week 2
Concentration of Aspartate aminotransferase (serum)	Measure of liver function	Week 6
Concentration of Aspartate aminotransferase (serum)	Measure of liver function	Week 12
Concentration of Aspartate aminotransferase (serum)	Measure of liver function	Week 24
Concentration of Thyroid Stimulating Hormone	Measure of thyroid activity	Week 2
Concentration of Thyroid Stimulating Hormone	Measure of thyroid activity	Week 6
Concentration of Thyroid Stimulating Hormone	Measure of thyroid activity	Week 12
Concentration of Thyroid Stimulating Hormone	Measure of thyroid activity	Week 24
Concentration of Calcitonin	Measure of bone formation	Week 12
Concentration of Osteocalcin	Measure of bone formation	Week 12
Concentration of Bone-Specific Alkaline Phosphatase	Measure of bone turnover	Week 12
Concentration of Procollagen Type I Intact N Terminal Propeptide (PINP)	Measure of bone formation	Week 12
Concentration of Collagen Type I C-Telopeptide (CTx)	Measure of bone resorption	Week 12
Coronary Artery Calcium Score	Composite Coronary Artery Calcium Score	Week 12
Coronary Artery Calcium Score	Composite Coronary Artery Calcium Score	Week 24
Prothrombin Time	Measure of blood coagulation	Week 2
Prothrombin Time	Measure of blood coagulation	Week 6
Prothrombin Time	Measure of blood coagulation	Week 12
Prothrombin Time	Measure of blood coagulation	Week 24
Internationalized Normalized Ratio	Measure of blood coagulation	Week 2
Internationalized Normalized Ratio	Measure of blood coagulation	Week 6
Internationalized Normalized Ratio	Measure of blood coagulation	Week 12
Internationalized Normalized Ratio	Measure of blood coagulation	Week 24

Collaborators and Investigators

• Sponsor: National University of Natural Medicine
• Investigators: Principal Investigator: Ryan Bradley, National University of Natural Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 16, 2022
• First Submitted That Met QC Criteria: March 29, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): August 7, 2024
• Last Update Submitted That Met QC Criteria: August 2, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: quality of life; atrial fibrillation; supplements; calcium; antiorbital ionic calcium
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease Attributes; Arrhythmias, Cardiac; Atrial Fibrillation; Chronic Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Antacids; Calcium; Calcium, Dietary; Calcium Carbonate
• Other Study ID Numbers: RB121521

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No