Muscle OXPHOS and Nutrient Homeostasis
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ClinicalTrials.gov Identifier: NCT02920671 |
Recruitment Status :
Active, not recruiting
First Posted : September 30, 2016
Last Update Posted : July 28, 2022
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Tracking Information | ||||
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First Submitted Date | September 27, 2016 | |||
First Posted Date | September 30, 2016 | |||
Last Update Posted Date | July 28, 2022 | |||
Actual Study Start Date | February 14, 2017 | |||
Actual Primary Completion Date | March 30, 2019 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures |
Glucose rate of disposal (glucose Rd) during OGTT* [ Time Frame: 1 day ] The primary outcome for the present study will be glucose rate of disposal (Rd) during the OGTT*
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Original Primary Outcome Measures | Same as current | |||
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Current Secondary Outcome Measures |
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Original Secondary Outcome Measures |
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Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures | Not Provided | |||
Descriptive Information | ||||
Brief Title | Muscle OXPHOS and Nutrient Homeostasis | |||
Official Title | Skeletal Muscle Oxidative Phosphorylation Capacity and Nutrient Homeostasis in Individuals With Primary (Genetic) and Secondary (Obesity-related) Mitochondrial Impairment as Compared to Healthy, Normal-weight Individuals | |||
Brief Summary | Investigators are recruiting adults (men and women, ages 18 to 65 years, inclusive) with a confirmed genetic diagnosis of mitochondrial disease. Investigators are also recruiting both obese and normal-weight healthy volunteers (men and women, ages 18 to 65 years, inclusive) without a family history of mitochondrial disease to compare to affected individuals. The study involves non-invasive MRI methods and glucose tests to focus on the relationship between mitochondrial disease, obesity, and the risk of diabetes. All study visit procedures will be completed within 2 days, which includes an overnight stay at the Hospital of the University of Pennsylvania. There are no study medications or sedations, and participants will be continually monitored during minimally-invasive procedures (e.g., blood draws). All participants will be able to receive compensation. Furthermore, it may be possible to provide reimbursement for travel, lodging, and meals for individuals with mitochondrial disease. Investigators hope that this research will contribute to the current knowledge of mitochondrial disease and that it will improve diagnostic and treatment approaches. |
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Detailed Description | Although obesity is a significant public health problem, why obesity leads to diabetes in some individuals but not others is poorly understood. Mitochondrial impairment, particularly in skeletal muscle with its high energy requirement, has been implicated in the pathogenesis of obesity-related insulin resistance. In addition, individuals with genetic disorders affecting mitochondrial function are at increased risk of diabetes. The proposed studies will investigate the association between skeletal muscle oxidative phosphorylation capacity (OXPHOS), which is a dimension of mitochondrial function, and glucose and lipid homeostasis in (i) individuals with genetic disorders of muscle mitochondrial function as compared to (ii) non-obese adults and (iii) otherwise healthy obese adults. During a single 2-day, 1-night study visit, investigators will use innovative, non-invasive magnetic resonance imaging-based methods of estimating skeletal muscle oxidative phosphorylation capacity, including post-exercise chemical exchange saturation transfer (CrCEST) recovery and 31-Phosphorus (31P) magnetic resonance spectroscopy (MRS) and muscle lipid content, including 1H magnetic resonance spectroscopy (MRS) and 3-point Dixon techniques, in conjunction with a tracer-enhanced oral glucose tolerance test (OGTT*) to measure overall insulin sensitivity and the selective effect of insulin on glucose disposal (Rd). The percentage suppression of endogenous glucose production by the oral glucose load (% suppression of Ra of endogenous glucose) will also be assessed. Infusion of a glycerol tracer permits assessment of lipolysis in both the fasting state, and also after the oral glucose load, such that the percentage suppression of lipolysis by the oral glucose load can also be calculated (% suppression of Ra of glycerol). In addition, the insulin and c-peptide minimal models will also be used to model pancreatic β-cell responsiveness to the oral glucose load and hepatic insulin extraction. |
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Study Type | Observational | |||
Study Design | Observational Model: Case-Control Time Perspective: Cross-Sectional |
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Target Follow-Up Duration | Not Provided | |||
Biospecimen | Retention: Samples With DNA Description: Blood will be collected as part of this protocol. Results from screening laboratory studies will be entered into the secure database, and copies will be sent to the participant, as well as his/her physician if s/he wishes. De-identified, specimens coded with the participant's ID number will be stored in anticipation of future studies. DNA/RNA will be extracted and stored pending future analyses to be specified (e.g., whole exome or mitochondrial DNA sequencing, gene expression studies). No results of genetic analyses will be included in the electronic medical record. Participants will not be informed of results. |
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Sampling Method | Non-Probability Sample | |||
Study Population | This study will enroll three groups of individuals (mitochondrial disease, obese, normal weight). | |||
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Intervention |
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Publications * | Not Provided | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status | Active, not recruiting | |||
Actual Enrollment |
45 | |||
Original Estimated Enrollment | Same as current | |||
Estimated Study Completion Date | June 30, 2023 | |||
Actual Primary Completion Date | March 30, 2019 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria | Inclusion Criteria: Indvidiuals who meet all of the following criteria are eligible for participation in the study:
For individuals with mitochondrial disease: Clinical history consistent with the diagnosis of mitochondrial disease, and molecular genetic diagnosis. To ensure consistency with other trials performed in mitochondrial disease, investigators will also ensure that participants meet the same set of previously published criteria. These include clinical features consistent with primary mitochondrial disease and molecular genetic proof of a pathogenic mutation in mtDNA or nDNA in a gene known to be associated with dysfunction of complexes I-V of the respiratory chain. Specifically, eligible participants must have defined mtDNA or nDNA mutations affecting subunits or assembly of these complexes that are associated with known clinical/pathological features, such as chronic progressive external ophthalmoplegia (CPEO), Kearns-Sayre, mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), mitochondrial encephalopathy and ragged red fibers (MERRF), neuropathy, ataxia and retinitis pigmentosa (NARP) or Leigh syndrome (45). Investigators will explicitly include individuals with Friedreich's Ataxia (46), a mutation in the mitochondrial protein frataxin, and those with mutations in respiratory chain complex II protein, succinate dehydrogenase (SDH). For normal weight participants: BMI < 25 kg/m2. These will be matched with subjects with mitochondrial disease by age, sex, estrogen status (women), and usual self-reported physical activity (as either sedentary or not, i.e., for sedentary, less than 30 minutes of moderate physical activity 5 days per week, or vigorous physical activity for 20 minutes 3 days per week). For obese participants: BMI > 30 kg/m2. These will be matched with subjects with mitochondrial disease by age, sex, estrogen status (women), and usual self-reported physical activity (as either sedentary or not, i.e., for sedentary, less than 30 minutes of moderate physical activity 5 days per week, or vigorous physical activity for 20 minutes 3 days per week). Exclusion Criteria: For all study groups (i.e., mitochondrial disease, normal weight, obese):
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Sex/Gender |
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Ages | 18 Years to 65 Years (Adult, Older Adult) | |||
Accepts Healthy Volunteers | Yes | |||
Contacts | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries | United States | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number | NCT02920671 | |||
Other Study ID Numbers | 825558 | |||
Has Data Monitoring Committee | No | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement | Not Provided | |||
Current Responsible Party | University of Pennsylvania | |||
Original Responsible Party | Same as current | |||
Current Study Sponsor | University of Pennsylvania | |||
Original Study Sponsor | Same as current | |||
Collaborators | Not Provided | |||
Investigators |
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PRS Account | University of Pennsylvania | |||
Verification Date | July 2022 |