Ignite Creation Date:
2024-05-06 @ 5:43 PM
Last Modification Date:
2024-10-26 @ 2:34 PM
Study NCT ID:
NCT05408559
Status:
RECRUITING
Last Update Posted:
2023-09-18
First Post:
2022-03-17
Brief Title:
Prevention of Age-associated Cardiac and Vascular Dysfunction Using Avmacol ES
Sponsor:
Texas Tech University Health Sciences Center
Organization:
Texas Tech University Health Sciences Center
Study Overview
Official Title:
Prevention of Age-associated Cardiac and Vascular Dysfunction Through Nrf2 Signaling Using the Nutritional Supplement Sulforaphane
Status:
RECRUITING
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CardiacAging
Brief Summary:
Our local IRB approved clinical studies seeking proof of principle for the hypothesis that SFN can be safely administered to humans at doses sufficient to protect age-associated cardiac dysfunctions Beneficial effects of SFN-therapy will be assessed by Pre- and post-intervention echocardiography and exercise endurance at 0 and 24 weeks Peripheral blood cells from treated and control subjects will be compared for mitochondrial respiratory function oxidative damage pro-inflammatory cytokines and expression of antioxidant anti-electrophile genes
Detailed Description:
Study Design We intend to include 200 individuals 100 men and 100 women 60 years with a diagnosis of heart failure with preserved ejection fraction HFpEF who are able to walk at least 500 feet to participate in a randomized controlled double blinded study with Sulforaphane SFN or placebo treatment for 24 weeks These potential subjects will be recruited in a randomized controlled double blinded pilot study comparing SFN to placebo The study will be conducted at the Texas Tech University Health Sciences Center and University Medical Center The trial is approved by our local IRB IRB NUMBER L22-024 IRB APPROVAL DATE 12142021 and will be registered at clinicaltrialsgov Well trained Nurses of Clinical Research Institute TTUHSC will receive placebo and test compound from supplier and will dispense them to test subjects
Sulforaphane and Placebo Information Processed SFN-rich extract will be purchased from Nutramax Laboratories Inc 2208 Lakeside Blvd Edgewood MD 21040 Caplets containing SFN-rich broccoli sprout extracts or placebo caplets containing microcrystalline cellulose will be obtained from from Nutramax Labs Study medication will be dispensed in sealed bottles with instructions to keep them in a household freezer The size of the caplet will be about the size of a 1000 mg Vit C pill about 2 cm in length The participants will be dosed based on weight in a double-blind fashion with identical appearing placebo or SFN caplets Participants will be instructed to take a daily dose for 24 weeks based on the participants weight Two caplets for individuals 100 lb three caplets for individuals 100-200 lb and four caplets for individuals 200 lb SFN Avmacol Extra Strength or placebo will be prescribed by a study physician and will be dispensed by the study coordinators at TTUHSC Lubbock Pill counts will be conducted to demonstrate compliance
The study medications will arrive pre-packaged and be stored in a refrigerator freezer in the TTUHSC Clinical Research Institute based on the manufacturer-based guidelines and dispensed to each participant at their baseline visit and at the 12 weeks visit Patients will be expected to maintain at least an 80 adherence to the medication regimen in the absence of prohibitive toxicity Adherence will be monitored through pill counts Subjects who do not meet 80 compliance when questioned with phone visits and at 12-week pill count will be instructed on the importance of taking the pills as directed but if they demonstrate less than 80 compliance on average for more than 2 in person andor phone study visits they will be withdrawn from the study and we will not use their data If side effects are noted patient will be asked to notify the study team of the same and will be evaluated within a suitable time frame based on severity of side effects
SFN is a safe natural isolate The doses that are used in this study as described above 30mgcaplet are considered adequate to maintain intended therapeutic drug levels while maintaining a simple study design without significant concerns for drug toxicity SFN has been used in several clinical trials from doses ranging from 2-200µmolday for 2-28 weeks in 25-80 years old subjects without significant side-effect or toxicity httpsclinicaltrialsgovct2resultstermsulforaphaneSearchSearch
Data Analysis and Statistical Considerations Data will be analyzed using SPSS 210 for Windows SPSS Inc Chicago IL Descriptive statistics and correlation analysis will be performed All results will be expressed as meanSE The significance of difference in mean values between groups will be examined using analysis of variance ANOVA or when the ANOVA assumptions are not fulfilled using the Mann-Whitney if two groups are to be compared or Kruskal Wallis if three or more groups are to be compared non-parametric test These tests will be followed by Tukeys HSD test for means or ranks if appropriate SPSS 210 For evaluating changes in cardiac function and LV mass over time a mixed-design ANOVA implemented with generalized linear models will be used A value of P 005 will be considered statistically significant
Power analysis The number of subjects per group is based on previous results from studies using anabolic agents in older adults The power analysis assuming an equal sample size and variability among the groups α005 80 power and 30 expected difference in means was found to be n100group this allows for an anticipated 10-20 attrition rate
Study visitsRoles of subjects Informed consent will be obtained from participants prior to any study procedures Before and after the intervention the subjects will be tested at the TTUHSCUMC Cardiology lab Lubbock Subjects will undergo baseline health screening which will include a health status questionnaire SF-36 which will be repeated at 12 and 24 weeks
Echocardiography Echocardiography will be performed at TTUHSCUMC Cardiology Lab using a commercially available echocardiography unit Vivid E9 GE Waukesha WI USA to assess left ventricular LV mass LV systolic and diastolic function as described previously at Baseline and 24 weeks visits Speckle tracking echocardiography will be used to assess global longitudinal strain at baseline and its response to treatment Echocardiography will be performed by registered sonographers and interpreted by a cardiologist with advanced training in echocardiography level 3 certified Both the sonographer and the interpreter will be blinded to treatment allocation
Response to exercise After resting echocardiogram is performed all subjects will be subjected to treadmill exercise test using the Bruce protocol at baseline 12 and 24 weeks Tests will be performed in a standard fashion and exercise capacity will be expressed in metabolic equivalents METS which are derived from standard published nomograms based on the time on the treadmill We will also perform the 6 minute walk test on a hard flat surface at baseline and 24 weeks to assess functional capacity
Muscle function Muscle function will be determined by established strength and endurance tests These are the treadmill tests above and the hand grip test Hand grip strength Hand grip strength will be measured at baseline 24 weeks using a Jamar hand dynamometer
Blood samples Approximately 10 ml of blood will be drawn from the participants before starting SFN or placebo at Baseline and 24 weeks using aseptic techniques Peripheral blood mononuclear cells will be isolated within 4 hours of blood draw from a portion of the blood to analyze the reactive oxygen species formation markers of oxidative damage inflammatory signals CRP IL-6 and IL-10 mRNA expression levels of Nrf2 target genes and Nrf2ARE binding As described
Assessment of oxidative damage Oxidative biomarkers in skeletal muscle such as 8-oxo-78-2-deoxyguanosine DNA and lipid peroxidation MDA will be measured by ELISA spectrophotometry Western blot analysis and immunohistochemistry utilizing commercially available kits and appropriate antibodies
Determination of antioxidantanti-electrophile mRNA levels by real-time polymerase chain reaction Total RNA will be isolated from skeletal muscle and peripheral blood mononuclear cells samples of study participants by the guanidinium thiocyanate method Complementary DNA will also be prepared using cDNA synthesis kit Thermo Scientific Waltham MA Real-time polymerase chain reactions qPCR will be performed in triplicate on a DNA Engine Opticon 2 Detection System MJ Research Waltham MA with the SYBR select Master mix from Applied Biosystems Grand Island NY
The complete blood count CBC and CMP tests will be used as a broad screening test If an adverse event occurs and the study physician thinks it is necessary for the patients safety these tests will be performed to determine an individuals general health status
Arterial function Pulse wave velocity is a marker of endothelial function and predicts cardiovascular events Subjects will undergo noninvasive arterial function testing at Baseline and 24 weeks using an FDA-approved device Sphygmocor XCEL at TTUHSCUMC cardiology lab
Study Population We will recruit up to 200 volunteers 100 men and 100 women 65 years with diagnosis of HFpEF HF symptoms with a normal EF Participants will be recruited from the Cardiology Clinic and by the use of the Clinical Research Institutes volunteer database advertisements notices andor media Examples include IRB approved flyers posted in public settings at TTUHSC the TTUHSC Cardiology Clinic and newspaper advertisement All advertisements and recruitment materials will be IRB approved Anyone contacting the research team in response to an advertisementflyer will be pre-screened for study eligibility We will consent volunteers to participate in a randomized controlled double blinded study with SFN or placebo treatment for 24 weeks
Sulforaphane and Placebo Information Processed SFN-rich extract will be purchased from Nutramax Laboratories Inc 2208 Lakeside Blvd Edgewood MD 21040 Caplets containing SFN-rich broccoli sprout extracts or placebo caplets containing microcrystalline cellulose will be obtained from from Nutramax Labs Study medication will be dispensed in sealed bottles with instructions to keep them in a household freezer The size of the caplet will be about the size of a 1000 mg Vit C pill about 2 cm in length The participants will be dosed based on weight in a double-blind fashion with identical appearing placebo or SFN caplets Participants will be instructed to take a daily dose for 24 weeks based on the participants weight Two caplets for individuals 100 lb three caplets for individuals 100-200 lb and four caplets for individuals 200 lb SFN Avmacol Extra Strength or placebo will be prescribed by a study physician and will be dispensed by the study coordinators at TTUHSC Lubbock Pill counts will be conducted to demonstrate compliance
The study medications will arrive pre-packaged and be stored in a refrigerator freezer in the TTUHSC Clinical Research Institute based on the manufacturer-based guidelines and dispensed to each participant at their baseline visit and at the 12 weeks visit Patients will be expected to maintain at least an 80 adherence to the medication regimen in the absence of prohibitive toxicity Adherence will be monitored through pill counts Subjects who do not meet 80 compliance when questioned with phone visits and at 12-week pill count will be instructed on the importance of taking the pills as directed but if they demonstrate less than 80 compliance on average for more than 2 in person andor phone study visits they will be withdrawn from the study and we will not use their data If side effects are noted patient will be asked to notify the study team of the same and will be evaluated within a suitable time frame based on severity of side effects
SFN is a safe natural isolate The doses that are used in this study as described above 30mgcaplet are considered adequate to maintain intended therapeutic drug levels while maintaining a simple study design without significant concerns for drug toxicity SFN has been used in several clinical trials from doses ranging from 2-200µmolday for 2-28 weeks in 25-80 years old subjects without significant side-effect or toxicity httpsclinicaltrialsgovct2resultstermsulforaphaneSearchSearch
Data Analysis and Statistical Considerations Data will be analyzed using SPSS 210 for Windows SPSS Inc Chicago IL Descriptive statistics and correlation analysis will be performed All results will be expressed as meanSE The significance of difference in mean values between groups will be examined using analysis of variance ANOVA or when the ANOVA assumptions are not fulfilled using the Mann-Whitney if two groups are to be compared or Kruskal Wallis if three or more groups are to be compared non-parametric test These tests will be followed by Tukeys HSD test for means or ranks if appropriate SPSS 210 For evaluating changes in cardiac function and LV mass over time a mixed-design ANOVA implemented with generalized linear models will be used A value of P 005 will be considered statistically significant
Power analysis The number of subjects per group is based on previous results from studies using anabolic agents in older adults The power analysis assuming an equal sample size and variability among the groups α005 80 power and 30 expected difference in means was found to be n100group this allows for an anticipated 10-20 attrition rate
Study visitsRoles of subjects Informed consent will be obtained from participants prior to any study procedures Before and after the intervention the subjects will be tested at the TTUHSCUMC Cardiology lab Lubbock Subjects will undergo baseline health screening which will include a health status questionnaire SF-36 which will be repeated at 12 and 24 weeks
Echocardiography Echocardiography will be performed at TTUHSCUMC Cardiology Lab using a commercially available echocardiography unit Vivid E9 GE Waukesha WI USA to assess left ventricular LV mass LV systolic and diastolic function as described previously at Baseline and 24 weeks visits Speckle tracking echocardiography will be used to assess global longitudinal strain at baseline and its response to treatment Echocardiography will be performed by registered sonographers and interpreted by a cardiologist with advanced training in echocardiography level 3 certified Both the sonographer and the interpreter will be blinded to treatment allocation
Response to exercise After resting echocardiogram is performed all subjects will be subjected to treadmill exercise test using the Bruce protocol at baseline 12 and 24 weeks Tests will be performed in a standard fashion and exercise capacity will be expressed in metabolic equivalents METS which are derived from standard published nomograms based on the time on the treadmill We will also perform the 6 minute walk test on a hard flat surface at baseline and 24 weeks to assess functional capacity
Muscle function Muscle function will be determined by established strength and endurance tests These are the treadmill tests above and the hand grip test Hand grip strength Hand grip strength will be measured at baseline 24 weeks using a Jamar hand dynamometer
Blood samples Approximately 10 ml of blood will be drawn from the participants before starting SFN or placebo at Baseline and 24 weeks using aseptic techniques Peripheral blood mononuclear cells will be isolated within 4 hours of blood draw from a portion of the blood to analyze the reactive oxygen species formation markers of oxidative damage inflammatory signals CRP IL-6 and IL-10 mRNA expression levels of Nrf2 target genes and Nrf2ARE binding As described
Assessment of oxidative damage Oxidative biomarkers in skeletal muscle such as 8-oxo-78-2-deoxyguanosine DNA and lipid peroxidation MDA will be measured by ELISA spectrophotometry Western blot analysis and immunohistochemistry utilizing commercially available kits and appropriate antibodies
Determination of antioxidantanti-electrophile mRNA levels by real-time polymerase chain reaction Total RNA will be isolated from skeletal muscle and peripheral blood mononuclear cells samples of study participants by the guanidinium thiocyanate method Complementary DNA will also be prepared using cDNA synthesis kit Thermo Scientific Waltham MA Real-time polymerase chain reactions qPCR will be performed in triplicate on a DNA Engine Opticon 2 Detection System MJ Research Waltham MA with the SYBR select Master mix from Applied Biosystems Grand Island NY
The complete blood count CBC and CMP tests will be used as a broad screening test If an adverse event occurs and the study physician thinks it is necessary for the patients safety these tests will be performed to determine an individuals general health status
Arterial function Pulse wave velocity is a marker of endothelial function and predicts cardiovascular events Subjects will undergo noninvasive arterial function testing at Baseline and 24 weeks using an FDA-approved device Sphygmocor XCEL at TTUHSCUMC cardiology lab
Study Population We will recruit up to 200 volunteers 100 men and 100 women 65 years with diagnosis of HFpEF HF symptoms with a normal EF Participants will be recruited from the Cardiology Clinic and by the use of the Clinical Research Institutes volunteer database advertisements notices andor media Examples include IRB approved flyers posted in public settings at TTUHSC the TTUHSC Cardiology Clinic and newspaper advertisement All advertisements and recruitment materials will be IRB approved Anyone contacting the research team in response to an advertisementflyer will be pre-screened for study eligibility We will consent volunteers to participate in a randomized controlled double blinded study with SFN or placebo treatment for 24 weeks
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None