Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| US Department of Veterans Affairs | FED |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Insulin resistance (IR) is an important contributor to increased cardiovascular disease risk in type 1 diabetes (T1D). The purpose of this study is to measure the effect of metformin on insulin sensitivity, vascular function and compliance, and mitochondrial function in T1D. The long term goal is to identify novel non-glycemic approaches to managing cardiovascular disease risk in T1D. The results of this study may validate a novel approach to T1D treatment that could significantly improve current management of cardiovascular disease risk in this high risk population.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug | Six week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, 500/1000 for one week, and then 1000mg twice daily for the remainder of the 6 week intervention. If uptitration is not tolerated, max dose will be max tolerated dose of at least 500 mg twice daily. |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin Sensitivity by Hyperinsulinemic Euglycemic Clamp | Determine the effect of metformin on insulin sensitivity in T1D. Reported measure is glucose infusion rate during hyperinsulinemic euglycemic clamp normalized to total body weight. For this measure, insulin was infused at 40 mU/m2 surface area. Blood sugar wass checked every 5 minutes and glucose infusion adjusted to maintain glucose level at 90 mg/dL for 2 hours. The glucose infusion rate for the final 30 minutes is reported as GIR (aka M-value or glucose disposal rate) in mg glucose/kg*min. A higher value corresponds to greater sensitivity to insulin. There is no strictly defined normal range. | End of each 6 week intervention period |
| Flow-mediated Brachial Artery Dilation | Measure of endothelial function by brachial ultrasound of the percent dilation after 5 minutes of occlusion. | End of each 6 week intervention period |
| Measure | Description | Time Frame |
|---|---|---|
| Arterial Stiffness by PWV | Pulse wave velocity by Sphygmacor as a measure of aortic stiffness in m/sec. | End of each 6 week intervention period |
| Arterial Stiffness by AI@75 | Augmentation index by Sphygmacor is a measure of aortic arterial stiffness. AI@75 is the ratio of augmented pressure/pulse pressure adjusted to a heart rate of 75. |
| Measure | Description | Time Frame |
|---|---|---|
| Vascular Markers: PAI-1 | PAI-1 exploratory thromobotic marker. | End of each 6 week intervention period |
| Vascular Markers: Exploratory | ICAM | End of each 6 week intervention period |
Inclusion Criteria:
Exclusion Criteria:
Any comorbid condition associated with:
inflammation,
insulin Resistance, or
dyslipidemia including:
Tobacco use;
Pregnancy or women who are breastfeeding;
Steroid use;
Scheduled strenuous physical activity >3 days a week;
Angina, known CAD, or any other cardiovascular or pulmonary disease;
A history of COPD or asthma;
Presence of systolic blood pressure >190 at rest or >250 with exercise, or diastolic pressure >95 at rest or >105 with exercise;
Untreated thyroid disease;
Proteinuria (urine protein >200 mg/dl) or a creatinine > 1.5 mg/dl (males) or 1.4 mg/dL (females), suggestive of severe renal disease;
Severe Proliferative retinopathy;
Niacin treatment;
Administration of experimental agent for T1D within 30 days prior to screening;
Recent (prior 6 months) or current metformin or thiazolidenedione use;
Hypoglycemia unawareness or recurrent severe hypoglycemia (no symptoms of hypoglycemia with FSBS<40 and episodes of this severity >1 per week);
Weight instability (weight change >5% in last 6 months);
History of any organ transplant, including islet cell transplant;
Current or prior infection with HIV, hepatitis B or hepatitis C or hepatic -insufficiency (AST or ALT > 2x the upper limits of normal);
Any condition, medical or otherwise that would, in the opinion of the investigator, prevent complete participation in the study, or that would pose a significant hazard to the subject;
History of substance abuse within the 12 months prior to screening.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Irene Schauer, MD, PhD | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado Denver | Aurora | Colorado | 80045 | United States |
3 participants screen failed before starting the study. 3 more participants withdrew after randomization, but before starting the study.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Metformin, Then Placebo | Metformin: Six week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, 500/1000 for one week, and then 1000mg twice daily for the remainder of the 6 week intervention. If uptitration is not tolerated, max dose will be max tolerated dose of at least 500 mg twice daily. Placebo: Six-week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, and then the higher dose (850 mg) for the remainder of the 6 week intervention. |
| FG001 | Placebo, Then Metformin | Placebo: Six-week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, and then the higher dose (850 mg) for the remainder of the 6 week intervention. Metformin: Six week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, 500/1000 for one week, and then 1000mg twice daily for the remainder of the 6 week intervention. If uptitration is not tolerated, max dose will be max tolerated dose of at least 500 mg twice daily. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Baseline information was collected for all participants for which outcome measure data was able to be collected. One subject only completed the placebo arm and is not included in paired t-tests.
Initial random order, double-blinded design was revised to placebo-metformin, single-blinded (participants) design due to concern for carryover effects from metformin.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Metformin, Then Placebo | Metformin: Six week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, 500/1000 for one week, and then 1000mg twice daily for the remainder of the 6 week intervention. If uptitration is not tolerated, max dose will be max tolerated dose of at least 500 mg twice daily. Placebo: Six-week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, and then the higher dose (850 mg) for the remainder of the 6 week intervention. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Insulin Sensitivity by Hyperinsulinemic Euglycemic Clamp | Determine the effect of metformin on insulin sensitivity in T1D. Reported measure is glucose infusion rate during hyperinsulinemic euglycemic clamp normalized to total body weight. For this measure, insulin was infused at 40 mU/m2 surface area. Blood sugar wass checked every 5 minutes and glucose infusion adjusted to maintain glucose level at 90 mg/dL for 2 hours. The glucose infusion rate for the final 30 minutes is reported as GIR (aka M-value or glucose disposal rate) in mg glucose/kg*min. A higher value corresponds to greater sensitivity to insulin. There is no strictly defined normal range. | Posted | Mean | Standard Deviation | mg/kg/min | End of each 6 week intervention period |
|
4 Months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Metformin | Metformin: Six week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, 500/1000 for one week, and then 1000mg twice daily for the remainder of the 6 week intervention. If uptitration is not tolerated, max dose will be max tolerated dose of at least 500 mg twice daily. |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Irene Schauer, MD | University of Colorado Denver | 3037241111 | clinicalresearchsupportcenter@ucdenver.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 10, 2015 | Jun 8, 2021 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D003920 | Diabetes Mellitus |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Placebo | Drug | Six-week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, and then the higher dose (850 mg) for the remainder of the 6 week intervention. |
|
| End of each 6 week intervention period |
| Mitochondrial Measures: Oxygen Consumption | Oxygen consumption rate with various substrates and max uncoupled O2 consumption. Measure is performed on permeabilized muscle fibers from biopsy tissue from the vastus lateralis using the Oroboros OxygraphO2k high resolution respirometer. State 3 is full coupled oxygen flux using PMG or PMGS (pyruvate, malate, glutamate, +/- succinate) or OCMS (octanyl carnitine, malate, +/- succinate) as substrates. state 4 is after addition of oligomycin to inhibit the ATP synthase and thus corresponds to the maximum leak state where O2 consumption is limited by the buildup of the proton gradient and can only proceed as fast as the protons can leak back across the membrane. FCCP is added as an uncoupler, allowing free leakage of protons across the inner membrane, and thus measures maximum possible O2 flux. There are no defined normal ranges, but higher state 3 and uncoupled flux indicate better mitochondrial function, while state 4 is needed to correct state 3 to the fully coupled flux. | End of each 6 week intervention period |
| Mitochondrial Measures: Protein Expression Levels of Electron Transport Chain Complexes | Mito content by Western Blotting of electron transport chain complexes I, II, III, and V. complex 1 utilizes NADH from pyruvate/malate/glutamate while complex II utilizes FADH from succinate. complex III is the cytochrome c reductase while complex V is the ATP synthase. | End of each 6 week intervention period |
| Inflammatory Marker: hsCRP | hsCRP (mg/L) by Beckman Coulter assay | End of each 6 week intervention period |
| Heart Rate Variability | measure of autonomic function: ratio of fastest to slowest heart rate during valsalva maneuver | End of each 6 week intervention period |
| Continuous Glucose Monitor Measures of Mean Glucose | Mean Glucose & Glucose Standard Deviation (Glycemic Variability) by Dexcom CGM | Last Week of each 6 Week Intervention Period (over 7 days) |
| Continuous Glucose Monitor Measures of Hypoglycemia | Percent of time less than 70 mg/dL during the final week of each phase by Dexcom CGM. | Last Week of each 6 Week Intervention Period (over 7 days) |
| Metabolic Markers: Glucagon | Glucagon (pg/ml); baseline on AM of each phase final study visit. | End of each 6 week intervention period |
| Metabolic Markers: Glucose, Triglycerides, Cholesterol | Glucose (mg/dL), triglycerides (mg/dL), cholesterol (mg/dL) at baseline after each phase | End of each 6 week intervention period |
| Metabolic Markers: Fatty Acids | fatty acids (microeq/L) at baseline after each phase in the AM of the final visit | End of each 6 week intervention period |
| Metabolic Markers: Glycerol | glycerol (micromol/L) at baseline after each phase in the AM of the final phase visit | End of each 6 week intervention period |
| Metabolic Markers: Insulin | insulin (microIU/ml) at baseline after each phase in the AM of the final phase visit | End of each 6 week intervention period |
| Metabolic Markers: Lactate | lactate (mmol/L) at baseline after each phase in the AM of the final phase visit | End of each 6 week intervention period |
| Metabolic Markers: Adiponection | adiponection (microg/ml) at baseline after each phase in the AM of the final phase visit | End of each 6 week intervention period |
| Vascular Markers: Endothelin-1 (pg/ml) | endothelin-1 at baseline after each phase in the AM of the final phase visit by peninsula labs radioimmunoassay | End of each 6 week intervention period |
| In Vivo Mitochondrial Function: Ratio of the Amount of ATP Generated Per Unit of Oxygen Consumed | Measured by 31P-mass spec. This ratio measures mitochondrial efficiency. The higher the ratio, the more efficiently the individual converts metabolic substrates into ATP, with the ATP then available for energy-demanding cellular processes such as protein synthesis and biomass production | End of each 6 week intervention period |
| In Vivo Mitochondrial Function: Time Constants | Measured by 31P-mass spec. ADP time constant and phosphocreatine time constant. ADP time constant is a measure of the time required to convert ADP → ATP and is a measure of muscle mitochondrial health (energy metabolism). A faster recovery is a better outcome; a slower recovery is a worse outcome. Similarly for phosphocreatine. | End of each 6 week intervention period |
| In Vivo Mitochondrial Function: QMax, VPCr | Measured by 31P-mass spec. For each measure, a higher value indicates better mitochondrial function. All re calculated from multiple measures from the MRS spectra. These are relatively new research measures and normal values are not known or generally accepted.
| End of each 6 week intervention period |
| In Vivo Mitochondrial Function: Oxidative Phosphorylation | Measured by 31P-mass spec. A higher value indicates better mitochondrial function. All re calculated from multiple measures from the MRS spectra. These are relatively new research measures and normal values are not known or generally accepted. Oxidative Phosphorylation measures the rate at which electron transport activity generates phosphorylated energy sources (ATP and PCr) | End of each 6 week intervention period |
| In Vivo Mitochondrial Function:AnGly | Measured by 31P-mass spec. Anaerobic glycolysis measures the amount of anaerobic ATP generation for energy. It is generally felt that a higher value here reflects impaired mitochondrial function necessitating greater reliance on anaerobic metabolism. | End of each 6 week intervention period |
| Cardiac Function | Cardiac output | End of each 6 week intervention period |
| Oxidative Stress Markers | TBARs, GSSG:GSH ratio | End of each 6 week intervention period |
| Mitochondrial Measures: Oxidant Generation | oxidant generation | End of each 6 week intervention period |
| Inflammatory Markers: Exploratory | IL6, TNF alpha | End of each 6 week intervention period |
| Mitochondrial Oxidant Generation | exploratory measure looking at H2O2 production. not performed due to equipment not available. | after each 6 week intervention |
| BG001 | Placebo, Then Metformin | Placebo: Six-week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, and then the higher dose (850 mg) for the remainder of the 6 week intervention. Metformin: Six week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, 500/1000 for one week, and then 1000mg twice daily for the remainder of the 6 week intervention. If uptitration is not tolerated, max dose will be max tolerated dose of at least 500 mg twice daily. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo | Placebo: Six-week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, and then the higher dose (850 mg) for the remainder of the 6 week intervention. |
|
|
| Primary | Flow-mediated Brachial Artery Dilation | Measure of endothelial function by brachial ultrasound of the percent dilation after 5 minutes of occlusion. | Not completed on last subjects -futility, concern re reliability, and difficulty getting US images analyzed. | Posted | Mean | Standard Deviation | percent change in BA diameter | End of each 6 week intervention period |
|
|
|
| Secondary | Arterial Stiffness by PWV | Pulse wave velocity by Sphygmacor as a measure of aortic stiffness in m/sec. | Posted | Mean | Standard Deviation | m/sec | End of each 6 week intervention period |
|
|
|
| Secondary | Arterial Stiffness by AI@75 | Augmentation index by Sphygmacor is a measure of aortic arterial stiffness. AI@75 is the ratio of augmented pressure/pulse pressure adjusted to a heart rate of 75. | Posted | Mean | Standard Deviation | ratio | End of each 6 week intervention period |
|
|
|
| Secondary | Mitochondrial Measures: Oxygen Consumption | Oxygen consumption rate with various substrates and max uncoupled O2 consumption. Measure is performed on permeabilized muscle fibers from biopsy tissue from the vastus lateralis using the Oroboros OxygraphO2k high resolution respirometer. State 3 is full coupled oxygen flux using PMG or PMGS (pyruvate, malate, glutamate, +/- succinate) or OCMS (octanyl carnitine, malate, +/- succinate) as substrates. state 4 is after addition of oligomycin to inhibit the ATP synthase and thus corresponds to the maximum leak state where O2 consumption is limited by the buildup of the proton gradient and can only proceed as fast as the protons can leak back across the membrane. FCCP is added as an uncoupler, allowing free leakage of protons across the inner membrane, and thus measures maximum possible O2 flux. There are no defined normal ranges, but higher state 3 and uncoupled flux indicate better mitochondrial function, while state 4 is needed to correct state 3 to the fully coupled flux. | Posted | Mean | Standard Deviation | pmoles/mg/s | End of each 6 week intervention period |
|
|
|
| Secondary | Mitochondrial Measures: Protein Expression Levels of Electron Transport Chain Complexes | Mito content by Western Blotting of electron transport chain complexes I, II, III, and V. complex 1 utilizes NADH from pyruvate/malate/glutamate while complex II utilizes FADH from succinate. complex III is the cytochrome c reductase while complex V is the ATP synthase. | Posted | Mean | Standard Deviation | Arbitrary units | End of each 6 week intervention period |
|
|
|
| Secondary | Inflammatory Marker: hsCRP | hsCRP (mg/L) by Beckman Coulter assay | Posted | Mean | Standard Deviation | mg/L | End of each 6 week intervention period |
|
|
|
| Secondary | Heart Rate Variability | measure of autonomic function: ratio of fastest to slowest heart rate during valsalva maneuver | Posted | Mean | Standard Deviation | ratio | End of each 6 week intervention period |
|
|
|
| Secondary | Continuous Glucose Monitor Measures of Mean Glucose | Mean Glucose & Glucose Standard Deviation (Glycemic Variability) by Dexcom CGM | Posted | Mean | Standard Deviation | mg/dL | Last Week of each 6 Week Intervention Period (over 7 days) |
|
|
|
| Secondary | Continuous Glucose Monitor Measures of Hypoglycemia | Percent of time less than 70 mg/dL during the final week of each phase by Dexcom CGM. | Posted | Mean | Standard Deviation | percentage of time | Last Week of each 6 Week Intervention Period (over 7 days) |
|
|
|
| Secondary | Metabolic Markers: Glucagon | Glucagon (pg/ml); baseline on AM of each phase final study visit. | NS by paired t-test | Posted | Mean | Standard Deviation | pg/ml | End of each 6 week intervention period |
|
|
|
| Secondary | Metabolic Markers: Glucose, Triglycerides, Cholesterol | Glucose (mg/dL), triglycerides (mg/dL), cholesterol (mg/dL) at baseline after each phase | Posted | Mean | Standard Deviation | mg/dL | End of each 6 week intervention period |
|
|
|
| Secondary | Metabolic Markers: Fatty Acids | fatty acids (microeq/L) at baseline after each phase in the AM of the final visit | Posted | Mean | Standard Deviation | microEq/L | End of each 6 week intervention period |
|
|
|
| Secondary | Metabolic Markers: Glycerol | glycerol (micromol/L) at baseline after each phase in the AM of the final phase visit | Posted | Mean | Standard Deviation | microM/L | End of each 6 week intervention period |
|
|
|
| Secondary | Metabolic Markers: Insulin | insulin (microIU/ml) at baseline after each phase in the AM of the final phase visit | Posted | Mean | Standard Deviation | microIU/ml | End of each 6 week intervention period |
|
|
|
| Secondary | Metabolic Markers: Lactate | lactate (mmol/L) at baseline after each phase in the AM of the final phase visit | Posted | Mean | Standard Deviation | mmoles/L | End of each 6 week intervention period |
|
|
|
| Secondary | Metabolic Markers: Adiponection | adiponection (microg/ml) at baseline after each phase in the AM of the final phase visit | Posted | Mean | Standard Deviation | microg/mL | End of each 6 week intervention period |
|
|
|
| Secondary | Vascular Markers: Endothelin-1 (pg/ml) | endothelin-1 at baseline after each phase in the AM of the final phase visit by peninsula labs radioimmunoassay | Posted | Mean | Standard Deviation | pg/mL | End of each 6 week intervention period |
|
|
|
| Secondary | In Vivo Mitochondrial Function: Ratio of the Amount of ATP Generated Per Unit of Oxygen Consumed | Measured by 31P-mass spec. This ratio measures mitochondrial efficiency. The higher the ratio, the more efficiently the individual converts metabolic substrates into ATP, with the ATP then available for energy-demanding cellular processes such as protein synthesis and biomass production | 2 subjects complete data for metformin, but not placebo. (images not good) ME not reported for one placebo subject due to AnGly out of range. | Posted | Mean | Standard Deviation | ratio | End of each 6 week intervention period |
|
|
|
| Secondary | In Vivo Mitochondrial Function: Time Constants | Measured by 31P-mass spec. ADP time constant and phosphocreatine time constant. ADP time constant is a measure of the time required to convert ADP → ATP and is a measure of muscle mitochondrial health (energy metabolism). A faster recovery is a better outcome; a slower recovery is a worse outcome. Similarly for phosphocreatine. | Posted | Mean | Standard Deviation | seconds | End of each 6 week intervention period |
|
|
|
| Secondary | In Vivo Mitochondrial Function: QMax, VPCr | Measured by 31P-mass spec. For each measure, a higher value indicates better mitochondrial function. All re calculated from multiple measures from the MRS spectra. These are relatively new research measures and normal values are not known or generally accepted.
| Posted | Mean | Standard Deviation | mmoles/sec | End of each 6 week intervention period |
|
|
|
| Secondary | In Vivo Mitochondrial Function: Oxidative Phosphorylation | Measured by 31P-mass spec. A higher value indicates better mitochondrial function. All re calculated from multiple measures from the MRS spectra. These are relatively new research measures and normal values are not known or generally accepted. Oxidative Phosphorylation measures the rate at which electron transport activity generates phosphorylated energy sources (ATP and PCr) | Posted | Mean | Standard Deviation | mmol/L/s | End of each 6 week intervention period |
|
|
|
| Secondary | In Vivo Mitochondrial Function:AnGly | Measured by 31P-mass spec. Anaerobic glycolysis measures the amount of anaerobic ATP generation for energy. It is generally felt that a higher value here reflects impaired mitochondrial function necessitating greater reliance on anaerobic metabolism. | One placebo subject out of range for AnGly | Posted | Mean | Standard Deviation | mmol/L/s | End of each 6 week intervention period |
|
|
|
| Secondary | Cardiac Function | Cardiac output | Posted | Mean | Standard Deviation | L/min | End of each 6 week intervention period |
|
|
|
| Other Pre-specified | Vascular Markers: PAI-1 | PAI-1 exploratory thromobotic marker. | this outcome not done-cost and assay issues | Posted | End of each 6 week intervention period |
|
|
| Other Pre-specified | Vascular Markers: Exploratory | ICAM | No outcome measure data was collected for this exploratory outcome measure due to insufficient funds. | Posted | End of each 6 week intervention period |
|
|
| Other Pre-specified | Oxidative Stress Markers | TBARs, GSSG:GSH ratio | This exploratory outcome measure was not collected | Posted | End of each 6 week intervention period |
|
|
| Other Pre-specified | Mitochondrial Measures: Oxidant Generation | oxidant generation | This exploratory outcome measure was not collected. | Posted | End of each 6 week intervention period |
|
|
| Other Pre-specified | Inflammatory Markers: Exploratory | IL6, TNF alpha | No data was collected for this exploratory outcome due to insufficient funds | Posted | End of each 6 week intervention period |
|
|
| Other Pre-specified | Mitochondrial Oxidant Generation | exploratory measure looking at H2O2 production. not performed due to equipment not available. | Not Posted | after each 6 week intervention | Participants |
| 0 |
| 16 |
| 0 |
| 16 |
| 0 |
| 16 |
| EG001 | Placebo | Placebo: Six-week intervention: Study drug/placebo will be given in a forced uptitration with 500 mg once daily for one week, 500 mg twice daily for one week, and then the higher dose (850 mg) for the remainder of the 6 week intervention. | 0 | 17 | 0 | 17 | 0 | 17 |
Not provided
Not provided
Not provided
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006946 | Hyperinsulinism |
| PMGS State 4 Oxygen Flux |
|
| PMGS Uncoupled Max Oxygen Flux |
|
| OCM State 3 Oxygen Flux |
|
| OCMS State 3 Oxygen Flux |
|
| OCMS State 4 Oxygen Flux |
|
| OCMS Uncoupled Max Oxygen Flux |
|
| complex III |
|
| complex V |
|
| total cholesterol |
|