QUICKENED: Quercetin for Cardio-Skeletal Muscle Health and Estrogen Deficiency

Sponsor

Wake Forest University Health Sciences (Other)

Overall Status

Suspended

CT.gov ID

NCT04258410

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Menopause Related Conditions	Drug: Placebo oral soft chew Drug: Quercetin	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double blind randomized controlled parallel pilot trial of Quercetin vs placebo oral administration in 24 postmenopausal women.Double blind randomized controlled parallel pilot trial of Quercetin vs placebo oral administration in 24 postmenopausal women.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Enrolled participants who complete the pre-treatment assessment will be randomly assigned to Quercetin or placebo. The trial manager who is not involved in any outcome assessments will carry out randomization following the protocol designed by the study biostatistician (Dr. Leng) prior to the study's start. The randomization sequence list will remain concealed from the investigators. Participants will be randomized using a computer-generated, password-protected randomization list, and simple randomization scheme. All staff involved in data collection and management will be kept unaware of the participants' group assignments and will explicitly inform participants that they (staff) are to remain blinded during the course of the study. The biostatistician will also be unaware of treatment assignment.

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Adherence: Percent adherence to study visits [20 weeks]
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.
Adherence: Percent adherence to intervention [20 weeks]
Participant treatment compliance will be determined by average plasma quercetin levels, in mg/dL, in each group.
Retention: Number of Subjects Lost to Follow Up [20 weeks]
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.
Retention: Number of Subjects Discontinued [20 weeks]
Participants that are prematurely terminated or discontinued from the study will be quantified. The circumstances that may warrant discontinuation will be evaluated and recorded.
Acceptability: Changes in patient satisfaction [Baseline and week 20]
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.

Other Outcome Measures

Changes in left ventricular systolic function [Baseline and 20 weeks]
Measure left ventricular ejection fraction (LVEF) by transthoracic echocardiogram (TTE), pre and post intervention
Changes in left ventricular diastolic function [Baseline and 20 weeks]
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
Changes in left ventricular filling pressure [Baseline and 20 weeks]
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
Changes in left ventricular (LV) structure [Baseline and 20 weeks]
Calculate LV mass and relative wall thickness from standard TTE images, pre and post intervention
Changes in left atrial structure [Baseline and 20 weeks]
Measure left atrial volume by TTE, pre and post intervention
Changes in skeletal muscle quality [Baseline and 20 weeks]
Echo-intensity, in pixels, of the vastus lateralis muscle of the thigh will be measured using ultrasound, pre and post intervention.
Changes in skeletal muscle composition [Baseline and 20 weeks]
Measure subcutaneous fat adjacent to vastus lateralis muscle by ultrasound, pre and post intervention
Changes in exercise capacity [Baseline and 20 weeks]
6-minute walk distance (6 MWD), pre and post intervention
Changes in skeletal muscle strength [Baseline and 20 weeks]
Five times sit-to-stand test, pre and post intervention
Changes in biomarker of inflammation [Baseline and 20 weeks]
Blood sample for measure of high-sensitivity C-reactive protein (hs-CRP), pre and post intervention
Changes in biomarker of oxidative stress [Baseline and 20 weeks]
Blood sample for determination of malondialdehyde by ELISA assay, pre and post intervention
Changes in biomarker of anti-oxidant defense [Baseline and 20 weeks]
Blood sample for glutathione levels using a commercial assay kit, pre and post intervention
Changes in biomarker of LV remodeling [Baseline and 20 weeks]
Blood sample for N terminal-ProBNP levels using the Roche Assay, pre and post intervention

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 74 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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