Quercetin for Cardio-Skeletal Muscle Health and Estrogen Deficiency (QUICKENED)

Quercetin for Cardio-Skeletal Muscle Health and Estrogen Deficiency (QUICKENED) Feasibility Study in Older Women

Double blind randomized controlled parallel pilot trial of Quercetin vs placebo oral administration in 24 postmenopausal women. The study team will conduct a feasibility pilot in preparation for a larger efficacy trial that will test the protective effects of quercetin against cardiac and skeletal muscle dysfunction and changes in structure induced by estrogen loss and potential mechanistic pathways in post-menopausal women at risk of heart failure with preserved ejection fraction (HFPEF).

Study Overview

• Status: Withdrawn
• Conditions: Menopause Related Conditions
• Intervention / Treatment: Drug: Placebo oral soft chew; Drug: Quercetin

Detailed Description

Participants receive either oral Quercetin 1000 g/day or placebo for 20 weeks. Quercetin levels, biomarkers, ultrasounds (heart and muscle), functional assessments will be measured on enrollment and after the intervention. The study coordinator will contact participants weekly to monitor safety and ensure compliance. All quercetin administration will be supervised by Claudia L Campos, MD, Associate Professor of Internal Medicine, Medical Director Internal Medicine clinic.

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 58 years to 72 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female, postmenopausal, aged 60 to 74
• Stated willingness to comply with all study procedures and availability for the duration of the study
• High risk of Heart failure with preserved ejection fraction (HFPEF) using web-based Primary Care Physician-HF risk tool (Khan S, et al.10-Year Risk Equations for Incident Heart Failure in the General Population. Information used for calculation include: age, gender, race, hypertension treatment (yes or no), fasting glucose value, smoking status, body mass index, systolic BP, diabetes treatment (yes or no), total cholesterol, HDL cholesterol, and electrocardiogram QRS duration. Prospective participant's with scores >= 10% will be included.
• Electrocardiogram (EKG) on medical record

Exclusion Criteria:

• History of congestive heart failure or use of loop diuretics
• Recent myocardial infarction (MI), stroke, angina, or atrial fibrillation (in the past 6 months), either self-reported and or in the electronic medical record.
• Uncontrolled diabetes mellitus
• Uncontrolled hypertension
• Significant renal insufficiency requiring dialysis or estimated glomerular filtration rate (eGFR) < 15 mL/min
• Liver disease
• Psychiatric disease - uncontrolled major psychoses, depressions, dementia, or personality disorder
• Participants reporting extreme energy intakes >3500 or <500 kcal/day
• Plans to leave area within the study period
• Refuses informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Blinded subjects in this arm will receive 2 placebo (blank) soft chews, twice daily, orally for 20 weeks.	Drug: Placebo oral soft chew; placebo identical to experimental drug contained in soft chew
Experimental: Active Drug; Blinded subjects in this arm will receive 1 g/day of Quercetin delivered in 2 soft chews (250 mg/chew), twice daily, orally, for 20 weeks.	Drug: Quercetin; experimental drug contained in soft chew; Other Names: Bioflavonoid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility: Number of enrolled participants per month	Proportion of eligible participants enrolled each month, over the course of recruitment.	up through 13 months
Eligibility: Proportion eligible after screening	Proportion of eligible participants that are invited to participate after initial screening and reasons for declining enrollment.	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence: Percent adherence to study visits	Missing data will be quantified, and reasons for failure to follow-up will be determined through informal comments from participants, via phone contact, to assess adherence barriers.	20 weeks
Adherence: Percent adherence to intervention	Participant treatment compliance will be determined by average plasma quercetin levels, in mg/dL, in each group.	20 weeks
Retention: Number of Subjects Lost to Follow Up	Missing data and drop-out will be quantified, and reasons for lost to follow up will be evaluated through informal comments from participants and Likert-ranked questions to assess participant perceptions of strengths and weaknesses of the study.	20 weeks
Retention: Number of Subjects Discontinued	Participants that are prematurely terminated or discontinued from the study will be quantified. The circumstances that may warrant discontinuation will be evaluated and recorded.	20 weeks
Acceptability: Changes in patient satisfaction	Likert-ranking to assess participant perceptions of the strengths and weaknesses of the study. Scores range from 1 to 5 with a higher score denoting a positive outcome.	Baseline and week 20

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in left ventricular systolic function	Measure left ventricular ejection fraction (LVEF) by transthoracic echocardiogram (TTE), pre and post intervention	Baseline and 20 weeks
Changes in left ventricular diastolic function	Measures of myocardial relaxation by early septal mitral annular velocity (e') via tissue Doppler, and early-to-late transmitral filling velocity ratios (E/A) via Doppler from transthoracic echocardiogram, pre and post intervention	Baseline and 20 weeks
Changes in left ventricular filling pressure	Calculate ratio of early transmitral filling (E)-to-mitral annular velocity (e'), or E/e', by Doppler-derived images from TTE, pre and post intervention	Baseline and 20 weeks
Changes in left ventricular (LV) structure	Calculate LV mass and relative wall thickness from standard TTE images, pre and post intervention	Baseline and 20 weeks
Changes in left atrial structure	Measure left atrial volume by TTE, pre and post intervention	Baseline and 20 weeks
Changes in skeletal muscle quality	Echo-intensity, in pixels, of the vastus lateralis muscle of the thigh will be measured using ultrasound, pre and post intervention.	Baseline and 20 weeks
Changes in skeletal muscle composition	Measure subcutaneous fat adjacent to vastus lateralis muscle by ultrasound, pre and post intervention	Baseline and 20 weeks
Changes in exercise capacity	6-minute walk distance (6 MWD), pre and post intervention	Baseline and 20 weeks
Changes in skeletal muscle strength	Five times sit-to-stand test, pre and post intervention	Baseline and 20 weeks
Changes in biomarker of inflammation	Blood sample for measure of high-sensitivity C-reactive protein (hs-CRP), pre and post intervention	Baseline and 20 weeks
Changes in biomarker of oxidative stress	Blood sample for determination of malondialdehyde by ELISA assay, pre and post intervention	Baseline and 20 weeks
Changes in biomarker of anti-oxidant defense	Blood sample for glutathione levels using a commercial assay kit, pre and post intervention	Baseline and 20 weeks
Changes in biomarker of LV remodeling	Blood sample for N terminal-ProBNP levels using the Roche Assay, pre and post intervention	Baseline and 20 weeks

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: Leanne Groban, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: February 4, 2020
• First Submitted That Met QC Criteria: February 4, 2020
• First Posted (Actual): February 6, 2020

Study Record Updates

• Last Update Posted (Actual): October 10, 2022
• Last Update Submitted That Met QC Criteria: October 5, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: skeletal muscle function; estrogen deficiency; post-menopause; cardiac diastolic function; skeletal muscle structure; cardiac structure
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antioxidants; Quercetin
• Other Study ID Numbers: IRB-PENDING-LG

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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