Ignite Creation Date:
2025-12-24 @ 2:09 PM
Ignite Modification Date:
2025-12-29 @ 3:55 AM
Study NCT ID:
NCT06930495
Status:
RECRUITING
Last Update Posted:
2025-07-31
First Post:
2025-03-31
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Effect of Adiposity on Muscle and Microvascular Function in HFpEF
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015431', 'term': 'Weight Loss'}, {'id': 'D009765', 'term': 'Obesity'}, {'id': 'D007249', 'term': 'Inflammation'}], 'ancestors': [{'id': 'D001836', 'term': 'Body Weight Changes'}, {'id': 'D001835', 'term': 'Body Weight'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D050177', 'term': 'Overweight'}, {'id': 'D044343', 'term': 'Overnutrition'}, {'id': 'D009748', 'term': 'Nutrition Disorders'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D010335', 'term': 'Pathologic Processes'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'CASE_CONTROL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 100}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2024-12-10', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2026-06-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-07-28', 'studyFirstSubmitDate': '2025-03-31', 'studyFirstSubmitQcDate': '2025-04-08', 'lastUpdatePostDateStruct': {'date': '2025-07-31', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-04-16', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-03-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Peak muscle perfusion during exercise', 'timeFrame': 'Pre intervention (Day 1)', 'description': 'Peak muscle perfusion (Aβ) during exercise will be assessed by Contrast enhanced ultrasound (CEU)'}, {'measure': 'Peak muscle perfusion during exercise', 'timeFrame': 'Post intervention (Post Day 1)', 'description': 'Peak muscle perfusion (Aβ) during exercise will be assessed by Contrast enhanced ultrasound (CEU)'}, {'measure': 'Single cell RNA sequencing of skeletal muscle', 'timeFrame': 'Pre intervention (Day 2)', 'description': 'Skeletal muscle biopsies will be taken from the vastus lateralis using the modified Bergstrom technique and immediately prepared for single cell RNA sequencing. Samples will be digested, filtered, washed and resuspended in freezing media and checked for concentration and viability before single cell RNA sequencing is performed'}, {'measure': 'Single cell RNA sequencing of skeletal muscle', 'timeFrame': 'Post intervention (Day 2)', 'description': 'Skeletal muscle biopsies will be taken from the vastus lateralis using the modified Bergstrom technique and immediately prepared for single cell RNA sequencing. Samples will be digested, filtered, washed and resuspended in freezing media and checked for concentration and viability before single cell RNA sequencing is performed'}, {'measure': 'Muscle to fat ratio of leg', 'timeFrame': 'Pre intervention (Day 3)', 'description': 'MRI of the leg will be performed to acquire clear visualization of fasciae separating different muscle groups and thus allowing for quantification of intermuscular fat (muscle:fat ratio)'}, {'measure': 'Peak change in microvascular perfusion from rest to exercise', 'timeFrame': 'Pre intervention (Day 3)', 'description': 'MRI of the leg will be performed utilizing the PIVOT sequence which will measure global and regional perfusion of blood to the muscles in the lower leg at rest and during exercise. the peak change will be reported as the change from baseline to peak exercise'}, {'measure': 'Muscle to fat ratio of leg', 'timeFrame': 'Post intervention (Day 3)', 'description': 'MRI of the leg will be performed utilizing the PIVOT sequence which will measure the change in perfusion of blood to the muscles in the lower leg from rest to during exercise'}, {'measure': 'Peak change in microvascular perfusion from rest to exercise', 'timeFrame': 'Post intervention (Day 3)', 'description': 'MRI of the leg will be performed utilizing the PIVOT sequence which will measure global and regional perfusion of blood to the muscles in the lower leg at rest and during exercise. the peak change will be reported as the change from baseline to peak exercise'}], 'secondaryOutcomes': [{'measure': 'Vascular function - endothelium dependent vasodilation', 'timeFrame': 'Pre intervention (Day1)', 'description': 'A small ultrasound probe will be placed over the brachial artery and a small blood pressure cuff will be positioned on the lower arm, just below the elbow. Images of the vessel will be continuously recorded for 1 min (baseline) before the cuff is inflated to a high pressure (220mmHg) for 5minutes and immediately after the cuff is deflated for 3 minutes. The change in brachial artery diameter following deflation of cuff from baseline will represent a marker of vascular function'}, {'measure': 'Vascular function - endothelium dependent vasodilation', 'timeFrame': 'Post intervention (Day 1)', 'description': 'A small ultrasound probe will be placed over the brachial artery and a small blood pressure cuff will be positioned on the lower arm, just below the elbow. Images of the vessel will be continuously recorded for 1 min (baseline) before the cuff is inflated to a high pressure (220mmHg) for 5minutes and immediately after the cuff is deflated for 3 minutes. The change in brachial artery diameter following deflation of cuff from baseline will represent a marker of vascular function'}, {'measure': 'Blood volume measurement', 'timeFrame': 'Pre intervention (Day1)', 'description': 'The carbon monoxide rebreathe technique will be performed to measure blood volume'}, {'measure': 'Blood volume measurement', 'timeFrame': 'Post intervention (Day 1)', 'description': 'The carbon monoxide rebreathe technique will be performed to measure blood volume'}, {'measure': '2min walk endurance test', 'timeFrame': 'Pre intervention (Day 2)', 'description': 'Participants will be asked to walk on a flat surface back and forth between 2 cones for 2minutes. the total distance covered (in meters) during the 2-minutes will be recorded as a marker of endurance'}, {'measure': 'Hand grip strength', 'timeFrame': 'Pre intervention (Day 2)', 'description': 'Participants will squeeze a handheld dynamometer as hard as they can to measure handgrip strength (in kg). This will be performed on both hands'}, {'measure': '2min walk endurance test', 'timeFrame': 'Post intervention (Day2)', 'description': 'Participants will be asked to walk on a flat surface back and forth between 2 cones for 2minutes. the total distance covered (in meters) during the 2-minutes will be recorded as a marker of endurance'}, {'measure': 'Hand grip strength', 'timeFrame': 'Post intervention (Day2)', 'description': 'Participants will squeeze a handheld dynamometer as hard as they can to measure handgrip strength (in kg). This will be performed on both hands'}, {'measure': 'Body composition', 'timeFrame': 'Pre intervention (Day 0)', 'description': 'measured using dual xray absorptiometry (DEXA) to get lean mass, muscle mass, body fat percentage'}, {'measure': 'Body composition', 'timeFrame': 'Post intervention (Day 1)', 'description': 'measured using dual xray absorptiometry (DEXA) to get lean mass, muscle mass, body fat percentage'}, {'measure': 'Apnea hypopnea index', 'timeFrame': 'Pre intervention (Day 2)', 'description': 'Participants will be given an at home sleep apnea test that is incorporated into a wrist-based wearable that enables non-invasive tracking of sleep apnea burden.\n\nSleep apnea will be determined from the apnea hypopnea index measured by the device. Apnea hypopnea index will be calculated as the average number of apneas or hypopneas that occurs per hour of sleep'}, {'measure': 'Apnea hypopnea index', 'timeFrame': 'Post intervention (Day 2)', 'description': 'Participants will be given an at home sleep apnea test that is incorporated into a wrist-based wearable that enables non-invasive tracking of sleep apnea burden.\n\nSleep apnea will be determined from the apnea hypopnea index measured by the device. Apnea hypopnea index will be calculated as the average number of apneas or hypopneas that occurs per hour of sleep'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['HFpEF', 'Weight loss', 'adiposity', 'inflammation', 'RNA sequencing', 'skeletal muscle'], 'conditions': ['Heart Failure With Preserved Ejection Fraction (HFPEF)']}, 'descriptionModule': {'briefSummary': 'This project is an observational study in patients with heart failure with preserved ejection fraction (HFpEF) who are candidates for treatment with weight loss medication to manage obesity or diabetes as part of their standard clinical care. This study will include multiple experimental visits before and after treatment (minimum 7 percent weight loss, between 9-12 months) to understand how increased adiposity and inflammation effects skeletal muscle and cardiovascular health and function and to examine the effect of medically directed weight loss on skeletal muscle health and exercise tolerance.\n\nThe objective of this study is to\n\n1. Define the mechanisms by which adiposity impairs exercise hemodynamics, microvascular function, and oxygen transport/utilization in patients with HFpEF.\n2. Determine if intensive medically directed weight loss can reduce microvascular inflammation and normalize exercise hemodynamics.\n3. Quantify the effect of medically directed weight loss on skeletal muscle function and catabolism.\n\nHypotheses\n\n1. Perfusion of subcutaneous adipose tissue disrupts blood flow distribution and impairs muscle microvascular perfusion and exercise hemodynamics.\n2. Extramyocellular muscular lipid deposition and microvascular endothelial inflammation is associated with reduced capillarity and impaired microvascular perfusions, while intramyocellular triglyceride content is associated with poor skeletal muscle oxidative capacity,\n3. Intensive weight loss will improve exercise hemodynamics, microvascular perfusion, and reduce muscular inflammation, and resistance training will augment these effects.', 'detailedDescription': 'Objective one will also include a cross-sectional comparison between HFpEF patients before treatment and non-HFpEF controls matched for age and hypertension'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': 'Group 1: Patients with HFpEF\n\n\\- UTSW HFpEF clinic: lead by Dr. Ambarish Pandey\n\nGroup 2: non-HFpEF controls\n\n* subjects in the UTSW volunteer research registry who meet inclusion/exclusion criteria\n* community outreach (emailers, word of mouth, referrals)', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\nGroup 1: Patients with HFpEF\n\n* Diagnosis of heart failure or clear heart failure hospitalization\n* Stable ejection fraction \\> 0.50\n* Objective evidence of elevated left ventricular filling pressure by one of the following i) pulmonary capillary wedge pressure ≥25 mmHg during supine cardiopulmonary exercise testing or ii) a change in pulmonary capillary wedge pressure of \\>15 mmHg during upright exercise\n* Must be candidates for pharmacological incretin-based directed intensive weight loss therapies as part of their SOC\n* BMI\\>32kg/m2\n* ≥45 years old\n* Incretin naïve for 6 months\n\nGroup 2: Non-HFpEF controls\n\n* Adults who do not have heart failure with preserved ejection fraction\n* Age ≥ 18 years\n\nExclusion Criteria:\n\nGroup 1\n\n* Prior history of reduced ejection fraction (\\<50%)\n* Infiltrative cardiomyopathy\n* NYHA Class IV chronic heart failure\n* Left bundle branch block\n* Unstable coronary artery disease\n* Uncontrolled arrhythmia\n* CKD 4 or higher\n* Currently taking incretin-based drugs (SGL2, GLP1)\n* Severe valvular heart disease\n* BMI \\> 50kg/m2\n* Other debilitating illness that would preclude participation\n* Any contra-indication to MRI\n* Any contra-indication to muscle biopsies.\n\nGroup 2\n\n* Age \\< 18 years\n* BMI \\> 50 kg/m2\n* Atrial fibrillation with poorly controlled heart rate\n* PDE5 inhibitor use\n* Severe valvular disease\n* Severe COPD\n* CKD 4 or higher\n* Currently taking incretin-based drugs (SGL2, GLP1)\n* Any contra-indication to MRI\n* Any contra-indication to muscle biopsies.'}, 'identificationModule': {'nctId': 'NCT06930495', 'briefTitle': 'The Effect of Adiposity on Muscle and Microvascular Function in HFpEF', 'organization': {'class': 'OTHER', 'fullName': 'University of Texas Southwestern Medical Center'}, 'officialTitle': 'The Effect of Adiposity on Muscle and Microvascular Function in HFpEF', 'orgStudyIdInfo': {'id': 'STU-2024-0279'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'HFpEF and Obesity Group', 'description': 'Patients with HFpEF (heart failure with preserved ejection fraction) and diabetes will undergo standard of care treatment using the most appropriate second-generation anti-diabetic drug that induces clinically significant weight loss after completing baseline (pre) testing.', 'interventionNames': ['Drug: Weight loss SOC Treatment with second generation anti-diabetic medications']}, {'label': 'Control Group (Non-HFpEF and Obesity)', 'description': 'Controls matched for age and hypertension'}], 'interventions': [{'name': 'Weight loss SOC Treatment with second generation anti-diabetic medications', 'type': 'DRUG', 'description': 'To determine the best incretin-based drug for the treatment \\[done as part of regular standard of care (SOC) treatment\\], participants will go to UTSW weight wellness clinic and undergo a comprehensive history and physical exam to evaluate their overall health. This information is used to create an individualized approach to the participants weight loss regimen. As part of the regimen, participants will receive guidance on initiating lifestyle modifications including diet and exercise and may be referred to a clinical psychologist for evaluation and management of factors like stress, anxiety and depression, and exercise which may influence their health behaviors and body weight.', 'armGroupLabels': ['HFpEF and Obesity Group']}]}, 'contactsLocationsModule': {'locations': [{'zip': '75390', 'city': 'Dallas', 'state': 'Texas', 'status': 'RECRUITING', 'country': 'United States', 'facility': 'University of Texas Southwestern Medical Center', 'geoPoint': {'lat': 32.78306, 'lon': -96.80667}}], 'centralContacts': [{'name': 'Sarah L Hissen, PhD', 'role': 'CONTACT', 'email': 'sarah.hissen@utsouthwestern.edu', 'phone': '214-345-8841'}, {'name': 'Christopher M Hearon Jr, PhD', 'role': 'CONTACT', 'email': 'christopher.hearon@utsouthwestern.edu', 'phone': '214-345--4624'}], 'overallOfficials': [{'name': 'Christopher M Hearon Jr, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Texas Southwestern Medical Center'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Texas Southwestern Medical Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Assistant Professor', 'investigatorFullName': 'Christopher Hearon', 'investigatorAffiliation': 'University of Texas Southwestern Medical Center'}}}}