- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05679596
Exogenous Ketosis During Bed Rest in Older Adults (KBR)
Ketone Bodies as Therapeutic Agents to Reduce the Harmful Effects of Bed Rest on Muscle Mass and Metabolic Health in Older Adults
The goal of this randomized, double-blind, parallel group interventional study is to evaluate the effect of ketone bodies on healthy older adults (65-85 y) during 5 days of bed rest. The main questions it aims to answer are:
Does supplementation of ketone bodies prevent the typical decline in muscle protein synthesis, muscle size, muscle function, insulin sensitivity, and muscle mitochondrial function that occurs in response to bed rest?
Researchers will compare ketone supplements (KET) to an energy matched control beverage (carbohydrates and fats) to see if the ketones can rescue the decline in muscle protein synthesis rates, muscle loss, muscle function, insulin sensitivity, and mitochondrial function due to 5 days of bed rest.
This may positively impact the heath of older adults subjected to bed rest.
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Quebec
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Montréal, Quebec, Canada, H4A 3J1
- Research Institute - McGill University Health Centre
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Healthy, male, and female, older adults.
- Healthy will be defined as screen by the 2020 PAR-Q+, medical screening questionnaire, GAQ, and COVID-19 symptom questionnaire patient screening.
- 'Older' will be defined as being 65-85 years of age.
- Participants are required to not engage in structured resistance training for at least 6 months prior to participation in the study.
- Participants are willing to abide by the compliance rules of this study.
Exclusion Criteria:
- Pre-menopausal females: Women must be postmenopausal having not menstruated for at least 1 year prior to study participation. Hormonal fluctuations associated with the menstrual cycle have been reported to alter protein metabolism and may influence indices of muscle protein synthesis and breakdown (69-71).
- BMI <18.5 or > 30 kg ∙ m-2.
- Self-reported regular tobacco use and vaping products.
- Self-reported illicit drug use (e.g., growth hormone, testosterone, etc.)
- Individuals who have participated in studies within the past year involving a stable isotope of 2H.
- A history of thrombosis, diagnosed with type 2 diabetes mellitus by physician or HbA1c values of > 7.0%, dementia, coronary artery disease, musculoskeletal/orthopedic disorders, and severe allergies.
- The use of medications known to modulate skeletal muscle metabolism (e.g., corticosteroids, hormone replacement therapy, non-steroidal anti-inflammatory drugs, metformin).
- The use of over-the-counter supplements (protein supplements, creatine, fish oil).
- Inability to adhere to any of the compliance rules judged by the principal investigator or medical doctor.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Exogenous ketone monoester (KET)
KET will be provided at a dose of 360 mg kg-1 body mass per serving at 2 servings per day between each main meal (ΔG®; TΔS Ltd, UK, Oxford, UK).
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Provided twice a day between meals.
Other Names:
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Active Comparator: Energy matched control (CON)
CON will be provided at a dose energy matched to the KET supplement and consist of both carbohydrate (i.e., fructose) and fat (i.e., corn and canola oil 50:50 ratio).
1/3 of the supplemental energy will come from carbohydrate while 2/3 will come from fat.
We have excluded protein from the CON supplement since it is well established to influence our primary outcome measure (MPS rates).
A non-caloric sweetener will also be added to the CON supplement.
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Provided twice a day between meals.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in integrated fractional synthesis rate (%/d) in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day 0-5 and day 5-10
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Integrative myofibrillar fractional synthesis rate will be calculated during baseline (day 0-5) and bed rest (day 5-10) phases.
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Day 0-5 and day 5-10
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in whole body insulin sensitivity in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day-3 and Day 10.
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Measurements taken in the fasted state before and after bed rest.
Will measure blood glucose and insulin concentration during a hyperinsulinemic-euglycemic clamp.
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Day-3 and Day 10.
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Changes in whole-body lean mass (kg) in response to bed rest with and without ketone monoester (KET) supplementation
Time Frame: Day-3 and Day 10.
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Measurements taken in the fasted state using dual-energy x-ray absorptiometry (DXA) following urinary void before and after bed rest.
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Day-3 and Day 10.
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Changes in leg lean mass (kg) in response to bed rest with and without ketone monoester (KET) supplementation
Time Frame: Day -3 and Day 10.
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Measurements taken in the fasted state using dual-energy x-ray absorptiometry (DXA) following urinary void before and after bed rest.
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Day -3 and Day 10.
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Changes in quadriceps muscle volume in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Measurements taken before and after bed rest via magnetic resonance imaging (MRI).
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Day -3 and Day 10.
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Changes in maximal voluntary isometric contraction (N/m) of the knee extensors in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Measurements taken before and after bed rest using a Biodex dynamometer.
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Day -3 and Day 10.
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Changes in handgrip strength (kg) in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Measurements taken before and after bed rest using a Jamar hand dynamometer.
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Day -3 and Day 10.
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Changes in physical performance (numerical score) as determined by short physical performance battery (SPPB) in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Measurements taken before and after bed rest
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Day -3 and Day 10.
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Changes in physical performance (numerical score) as determined by 5-item physical performance test in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Measurements taken before and after bed rest
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Day -3 and Day 10.
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Changes in cognitive status in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day 4 and Day 9.
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NIH Toolbox Cognition Battery (computerized).
Measurements taken before and after bed rest
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Day 4 and Day 9.
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Changes in markers of inflammation in systemic circulation in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Markers of inflammation including: IL-1 beta, NF-K beta 1, IL-6, TNF-alpha, IFNY, MIP-1 beta will be evaluated.
Measurements taken before, during, and after bed rest.
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Day -3 and Day 10.
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Changes in muscle mRNA expression of inflammatory regulators will be assessed in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Muscle mRNA expression of NFKB1, TLR-4,IL-6, TNF-alpha, and IL-1Beta will be evaluated.
Measurements taken before and after bed rest
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Day -3 and Day 10.
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Changes in skeletal muscle phenotype in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Muscle cross-sections immunolabeled for type I, IIa, and IIx myosin heavy chains.
Measurements taken before and after bed rest.
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Day -3 and Day 10.
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Changes in skeletal muscle fiber size in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Muscle cross-sections analyzed for cross-sectional area.
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Day -3 and Day 10.
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Changes in mitochondrial content in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Via the assessment in succinate dehydrogenase activity.
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Day -3 and Day 10.
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Changes in mitochondrial respiration in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Assessed using standard substrate and inhibitor addition protocols in O2k high resolution Respirometer.
Measurements taken before and after bed rest.
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Day -3 and Day 10.
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Changes in mitochondrial calcium retention capacity (marker of mitochondrial propensity to trigger apoptosis) in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Determined spectrofluorometrically using the Calcium Green probe.
Measurements taken before and after bed rest.
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Day -3 and Day 10.
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Changes in mitochondrial reactive oxygen species (ROS) production in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Assessed using standard substrate and inhibitor addition protocols in O2k high resolution Respirometer.
Measurements taken before and after bed rest.
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Day -3 and Day 10.
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Changes in mitochondrial time to the permeability transition pore opening (marker of mitochondrial propensity to trigger apoptosis) in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Determined spectrofluorometrically using the Calcium Green probe.
Measurements taken before and after bed rest.
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Day -3 and Day 10.
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Changes in the phosphorylation status of anabolic signaling molecules modulating muscle protein synthesis (MPS) in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Western blotting - membranes will be probed with phospho-specific antibodies against IRS-1S527/Thr446, AktSer473, mTORSer2448, 4E-BP1Thr37/46, rpS6Ser240/244, p70S6KThr389.
Measurements taken before and after bed rest.
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Day -3 and Day 10.
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Changes in the phosphorylation status of catabolic signaling molecules modulating muscle protein breakdown (MPB) in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Western blotting - membranes will be probed with phospho-specific antibodies against FoxO3aThr32, MuRF1, and MAFbx.
Measurements taken before and after bed rest.
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Day -3 and Day 10.
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Blood beta-hydroxybutyrate concentrations (mmol/L) in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day 5 and Day 10
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Measurements taken at the start and end of bed rest.
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Day 5 and Day 10
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Changes in subjective pain via visual analog scale in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day 5-10.
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Throughout the 5 day bed rest period.
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Day 5-10.
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Changes in muscle area in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Peripheral quantitative computed tomography (pQCT).
Measurements taken before and after bed rest.
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Day -3 and Day 10.
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Changes in muscle density in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Peripheral quantitative computed tomography (pQCT).
Measurements taken before and after bed rest.
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Day -3 and Day 10.
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2H enrichments in body water before and during bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -1 to Day 10.
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Throughout the baseline and bed rest period.
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Day -1 to Day 10.
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2H-alanine enrichment in venous blood before and during bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -1 to Day 10.
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Throughout the baseline and bed rest period.
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Day -1 to Day 10.
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Changes in resting metabolic rate (RMR) in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day -3 and Day 10.
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Measurements taken before and after bed rest.
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Day -3 and Day 10.
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Physical activity level via accelerometer before bed rest.
Time Frame: Day 0-4.
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Throughout the baseline period
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Day 0-4.
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Changes in sleep disturbance (numerical score) during bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day 5-10.
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Via Patient-Reported Outcomes Measurement Information System (PROMIS) Short form 8a. Measured throughout the 5 day bed rest period.
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Day 5-10.
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Changes in sleep quality (numerical score) during bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day 5-10.
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Via Pittsburgh Sleep Quality Index (PSQI).
Measured throughout the 5 day bed rest period.
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Day 5-10.
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Average habitual dietary intake assessed using Keenoa for 3 days (a food tracker application).
Time Frame: Measured before bed rest.
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Dietary intake will be assessed for total energy (kcals) and macronutrient (protein, carbohydrate, and fat consumption; g) intake.
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Measured before bed rest.
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Changes in Thigh Absolute Synthetic Rate (ASR) in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day 0-5 and day 5-10
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Changes in Thigh Absolute Synthetic Rate (ASR) will be calculated during baseline (day 0-5) and bed rest (day 5-10) phases.
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Day 0-5 and day 5-10
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Changes in Thigh Absolute Protein Breakdown Rate (ABR) in response to bed rest with and without ketone monoester (KET) supplementation.
Time Frame: Day 0-5 and day 5-10
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Changes in Thigh Absolute Protein Breakdown Rate (ABR) will be calculated during baseline (day 0-5) and bed rest (day 5-10) phases.
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Day 0-5 and day 5-10
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Tyler A Churchward-Venne, PhD, McGill University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 427929
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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