Physical Function During ARSI Treatment

Advanced Prostate Carcinoma Clinical Trial

Official title:

Assessing Physical Function Following Androgen Receptor Signaling Inhibitor Treatment for Metastatic Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05612880
• Other study ID #: LCCC2214
• Status: Recruiting
• Start date: October 13, 2022
• Est. completion date: January 31, 2025

Study information

• Verified date: November 2023
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: Erik D Hanson, PhD
• Phone: 9199620816
• Email: edhanson[@]email.unc.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This single arm observational pilot study aims to determine the longitudinal effects of androgen receptor signaling inhibitors (ARSI) in men with advanced prostate cancer. The primary outcome for this trial is physical function, which will be evaluated at baseline, 12 and 24 weeks. Secondary outcomes including body composition, muscle function, balance, arterial stiffness and patient reported outcomes.

Description:

The purpose of this pilot trial is to obtain objective measurements of physical function in men with metastatic prostate cancer (mPC) initiating ARSI treatment at baseline, 12, and 24 weeks later. Grip strength, muscular power, body composition, balance, arterial stiffness, along with QoL, fatigue, anxiety, and depression will also be measured. Finally, the potential associations in primary and secondary outcomes by the type of ARSI, stage of mPC, and physical activity levels will be explored. With more men requiring ARSI treatment for metastatic castrate resistant prostate cancer (mCRPC), as well as being an efficacious option earlier in metastatic castrate sensitive prostate cancer (mCSPC), accurate estimates of declines from ARSI initiation are required to determine the true effects. Utilizing novel assessments in mPC like muscular power tests will provide insight into potentially more relevant assessments and outcomes to intervene on. The data from this pilot study will also determine effect sizes to adequately power future studies.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: January 31, 2025
• Est. primary completion date: October 12, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
• Subjects is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.
• Age = 18 years at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Diagnosis of metastatic disease from prostate cancer, or recurrent disease following definitive local therapy of prostate cancer, as assessed by their clinician
• Initiation of an ARSI (e.g., abiraterone, enzalutamide, apalutamide, or darolutamide) for mPC with concurrent androgen deprivation therapy (ADT).
• Availability to begin baseline testing within 8 weeks of ARSI treatment initiation.
• Physician clearance to perform physical assessments.
• Ability to speak and read English.

Exclusion Criteria:

• Prior ARSI treatment
• Current chemotherapy
• History of bone fractures or musculoskeletal injuries
• Neurological conditions that affect balance and/or muscle strength
• Intention to leave the region prior to completion of study
• Dementia, altered mental status or any psychiatric condition prohibiting the understanding or rendering of informed consent

Related Conditions & MeSH terms

• Advanced Prostate Carcinoma
• Prostatic Neoplasms

Intervention

Drug:
• androgen receptor signaling inhibitors
Prior to or within 8 weeks of ARSI initiation, men with advanced prostate cancer will perform baseline testing, with follow ups at 12 and 24 weeks

Locations

Country	Name	City	State
United States	Lineberger Comprehensive Cancer Center at University of North Carolina, Chapel Hill	Chapel Hill	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Self-Reported Physical Activity Levels	Physical activity levels will be determined using the Godin Leisure-Time Exercise questionnaire, a 1-page form that categorizes the number of minimal, moderate, and strenuous bouts of exercise lasting more than 15 minutes. Higher scores represent higher activity levels.	Baseline
Other	Self-Reported Physical Activity Levels	Physical activity levels will be determined using the Godin Leisure-Time Exercise questionnaire, a 1-page form that categorizes the number of minimal, moderate, and strenuous bouts of exercise lasting more than 15 minutes. Higher scores represent higher activity levels.	12 weeks
Other	Self-Reported Physical Activity Levels	Physical activity levels will be determined using the Godin Leisure-Time Exercise questionnaire, a 1-page form that categorizes the number of minimal, moderate, and strenuous bouts of exercise lasting more than 15 minutes. Higher scores represent higher activity levels.	24 weeks
Other	Physical Activity: accelerometry	Physical Activity will be quantified using accelerometers that will be worn continuously for ~1 wk after each visit to quantify sedentary, low, medium and high levels of activity.	Baseline
Other	Physical Activity: accelerometry	Physical Activity will be quantified using accelerometers that will be worn continuously for ~1 wk after each visit to quantify sedentary, low, medium and high levels of activity.	12 weeks
Other	Physical Activity: accelerometry	Physical Activity will be quantified using accelerometers that will be worn continuously for ~1 wk after each visit to quantify sedentary, low, medium and high levels of activity.	24 weeks
Primary	Physical function: 400m Walk	The time to walk 400m (in sec) will be performed as an indicator of walking endurance. A lower total time (and therefore higher gait speed) indicates greater cardiorespiratory capacity.	Baseline
Primary	Physical function: 400m Walk	The time to walk 400m (in sec) will be performed as an indicator of walking endurance. A lower total time (and therefore higher gait speed) indicates greater cardiorespiratory capacity.	12 weeks
Primary	Physical function: 400m Walk	The time to walk 400m (in sec) will be performed as an indicator of walking endurance. A lower total time (and therefore higher gait speed) indicates greater cardiorespiratory capacity.	24 weeks
Primary	Physical function: Timed Up and Go	The time to complete (in sec) the 2.44m (8 ft) timed up and go test will be performed as an indicator of agility, balance, and physical function. A lower total time is indicative of greater performance.	Baseline
Primary	Physical function: Timed Up and Go	The time to complete (in sec) the 2.44m (8 ft) timed up and go test will be performed as an indicator of agility, balance, and physical function. A lower total time is indicative of greater performance.	12 weeks
Primary	Physical function: Timed Up and Go	The time to complete (in sec) the 2.44m (8 ft) timed up and go test will be performed as an indicator of agility, balance, and physical function. A lower total time is indicative of greater performance.	24 weeks
Primary	Physical function: Short physical performance battery	The short physical performance battery (SPPB) is a group of measures that combines the results of the gait speed, chair stand and balance tests. It has been used as a predictive tool for possible disability and can aid in the monitoring of function in older people. The scores range from 0 (worst performance) to 12 (best performance). The SPPB has been shown to have predictive validity showing a gradient of risk for mortality, nursing home admission, and disability. Clinically meaningful changes are 0.3-1.0 points.	Baseline
Primary	Physical function: Short physical performance battery	The short physical performance battery (SPPB) is a group of measures that combines the results of the gait speed, chair stand and balance tests. It has been used as a predictive tool for possible disability and can aid in the monitoring of function in older people. The scores range from 0 (worst performance) to 12 (best performance). The SPPB has been shown to have predictive validity showing a gradient of risk for mortality, nursing home admission, and disability. Clinically meaningful changes are 0.3-1.0 points.	12 weeks
Primary	Physical function: Short physical performance battery	The short physical performance battery (SPPB) is a group of measures that combines the results of the gait speed, chair stand and balance tests. It has been used as a predictive tool for possible disability and can aid in the monitoring of function in older people. The scores range from 0 (worst performance) to 12 (best performance). The SPPB has been shown to have predictive validity showing a gradient of risk for mortality, nursing home admission, and disability. Clinically meaningful changes are 0.3-1.0 points.	24weeks
Secondary	Body composition: lean mass	To report total body lean mass using dual-energy x-ray absorptiometry (DXA).	Baseline
Secondary	Body composition: lean mass	To report total body lean mass using dual-energy x-ray absorptiometry (DXA).	12 weeks
Secondary	Body composition: lean mass	To report total body lean mass using dual-energy x-ray absorptiometry (DXA).	24 weeks
Secondary	Body composition: fat mass	To report total body fat mass using dual-energy x-ray absorptiometry (DXA).	Baseline
Secondary	Body composition: fat mass	To report total body fat mass using dual-energy x-ray absorptiometry (DXA).	12 weeks
Secondary	Body composition: fat mass	To report total body fat mass using dual-energy x-ray absorptiometry (DXA).	24 weeks
Secondary	Body composition: bone mass	To report total body bone mass using dual-energy x-ray absorptiometry (DXA).	Baseline
Secondary	Body composition: bone mass	To report total body bone mass using dual-energy x-ray absorptiometry (DXA).	12 weeks
Secondary	Body composition: bone mass	To report total body bone mass using dual-energy x-ray absorptiometry (DXA).	24weeks
Secondary	Body composition: thigh muscle cross-sectional area	Muscle size will be analyzed using ultrasound of the vastus lateralis of the dominant leg. Higher muscle mass and quality are associated with greater muscle strength, physical function, QoL, and mortality.	Baseline
Secondary	Body composition: thigh muscle cross-sectional area	Muscle size will be analyzed using ultrasound of the vastus lateralis of the dominant leg. Higher muscle mass and quality are associated with greater muscle strength, physical function, QoL, and mortality.	12 weeks
Secondary	Body composition: thigh muscle cross-sectional area	Muscle size will be analyzed using ultrasound of the vastus lateralis of the dominant leg. Higher muscle mass and quality are associated with greater muscle strength, physical function, QoL, and mortality.	24 weeks
Secondary	Body composition: thigh muscle quality	Muscle architecture will be analyzed using ultrasound of the vastus lateralis of the dominant leg. Higher muscle mass and quality are associated with greater muscle strength, physical function, QoL, and mortality. Muscle quality is reported in arbitrary units, where a lower value indicates a higher/better muscle quality.	Baseline
Secondary	Body composition: thigh muscle quality	Muscle architecture will be analyzed using ultrasound of the vastus lateralis of the dominant leg. Higher muscle mass and quality are associated with greater muscle strength, physical function, QoL, and mortality. Muscle quality is reported in arbitrary units, where a lower value indicates a higher/better muscle quality.	12 weeks
Secondary	Body composition: thigh muscle quality	Muscle architecture will be analyzed using ultrasound of the vastus lateralis of the dominant leg. Higher muscle mass and quality are associated with greater muscle strength, physical function, QoL, and mortality. Muscle quality is reported in arbitrary units, where a lower value indicates a higher/better muscle quality.	24 weeks
Secondary	Body composition: skeletal muscle	CT scans will also be performed to assess skeletal muscle (SM). The L3 scan is uploaded into a software called SliceOmatic (TomoVision, Montreal, Quebec, Canada) to segment L3 into cross-sectional SM area, SAT area, and VAT area based on Hounsfield Units (HU) ranges: -29 to 150 for SM. An add-on module called Automated Body composition Analyzer using Computed tomography image Segmentation (ABACS) automatically performs the segmentation and produces an unbiased estimation.	Baseline
Secondary	Body composition: skeletal muscle	CT scans will also be performed to assess skeletal muscle (SM). The L3 scan is uploaded into a software called SliceOmatic (TomoVision, Montreal, Quebec, Canada) to segment L3 into cross-sectional SM area, SAT area, and VAT area based on Hounsfield Units (HU) ranges: -29 to 150 for SM. An add-on module called Automated Body composition Analyzer using Computed tomography image Segmentation (ABACS) automatically performs the segmentation and produces an unbiased estimation.	12 weeks
Secondary	Body composition: skeletal muscle	CT scans will also be performed to assess skeletal muscle (SM). The L3 scan is uploaded into a software called SliceOmatic (TomoVision, Montreal, Quebec, Canada) to segment L3 into cross-sectional SM area, SAT area, and VAT area based on Hounsfield Units (HU) ranges: -29 to 150 for SM. An add-on module called Automated Body composition Analyzer using Computed tomography image Segmentation (ABACS) automatically performs the segmentation and produces an unbiased estimation.	24 weeks
Secondary	Body composition: subcutaneous adipose tissue	CT scans will also be performed to subcutaneous adipose tissue (SAT). The L3 scan is uploaded into a software called SliceOmatic (TomoVision, Montreal, Quebec, Canada) to segment L3 into cross-sectional SM area, SAT area, and VAT area based on Hounsfield Units (HU) ranges: -190 to -30 for SAT. An add-on module called Automated Body composition Analyzer using Computed tomography image Segmentation (ABACS) automatically performs the segmentation and produces an unbiased estimation.	Baseline
Secondary	Body composition: subcutaneous adipose tissue	CT scans will also be performed to subcutaneous adipose tissue (SAT). The L3 scan is uploaded into a software called SliceOmatic (TomoVision, Montreal, Quebec, Canada) to segment L3 into cross-sectional SM area, SAT area, and VAT area based on Hounsfield Units (HU) ranges: -190 to -30 for SAT. An add-on module called Automated Body composition Analyzer using Computed tomography image Segmentation (ABACS) automatically performs the segmentation and produces an unbiased estimation.	12 weeks
Secondary	Body composition: subcutaneous adipose tissue	CT scans will also be performed to subcutaneous adipose tissue (SAT). The L3 scan is uploaded into a software called SliceOmatic (TomoVision, Montreal, Quebec, Canada) to segment L3 into cross-sectional SM area, SAT area, and VAT area based on Hounsfield Units (HU) ranges: -190 to -30 for SAT. An add-on module called Automated Body composition Analyzer using Computed tomography image Segmentation (ABACS) automatically performs the segmentation and produces an unbiased estimation.	24 weeks
Secondary	Body composition: visceral adipose tissue	CT scans will also be performed to assess visceral adipose tissue (VAT). The L3 scan is uploaded into a software called SliceOmatic (TomoVision, Montreal, Quebec, Canada) to segment L3 into cross-sectional SM area, SAT area, and VAT area based on Hounsfield Units (HU) ranges: -150 to -50 for VAT. An add-on module called Automated Body composition Analyzer using Computed tomography image Segmentation (ABACS) automatically performs the segmentation and produces an unbiased estimation.	Baseline
Secondary	Body composition: visceral adipose tissue	CT scans will also be performed to assess visceral adipose tissue (VAT). The L3 scan is uploaded into a software called SliceOmatic (TomoVision, Montreal, Quebec, Canada) to segment L3 into cross-sectional SM area, SAT area, and VAT area based on Hounsfield Units (HU) ranges: -150 to -50 for VAT. An add-on module called Automated Body composition Analyzer using Computed tomography image Segmentation (ABACS) automatically performs the segmentation and produces an unbiased estimation.	12 weeks
Secondary	Body composition: visceral adipose tissue	CT scans will also be performed to assess visceral adipose tissue (VAT). The L3 scan is uploaded into a software called SliceOmatic (TomoVision, Montreal, Quebec, Canada) to segment L3 into cross-sectional SM area, SAT area, and VAT area based on Hounsfield Units (HU) ranges: -150 to -50 for VAT. An add-on module called Automated Body composition Analyzer using Computed tomography image Segmentation (ABACS) automatically performs the segmentation and produces an unbiased estimation.	24 weeks
Secondary	Grip Strength	Grip strength will be assessed using a handgrip dynamometer. Grip strength is based on the maximal voluntary contraction of the subject's upper body muscles. One practice repetition is performed on each side. Three trials are performed on each side, alternating sides after every repetition. The maximal grip score from all six trials is recorded.	Baseline
Secondary	Grip Strength	Grip strength will be assessed using a handgrip dynamometer. Grip strength is based on the maximal voluntary contraction of the subject's upper body muscles. One practice repetition is performed on each side. Three trials are performed on each side, alternating sides after every repetition. The maximal grip score from all six trials is recorded.	12 weeks
Secondary	Grip Strength	Grip strength will be assessed using a handgrip dynamometer. Grip strength is based on the maximal voluntary contraction of the subject's upper body muscles. One practice repetition is performed on each side. Three trials are performed on each side, alternating sides after every repetition. The maximal grip score from all six trials is recorded.	24 weeks
Secondary	Muscle Power	Muscular power will be assessed using a linear position transducer (LPT). A sit-to-stand (STS) power test will be performed. Two practice repetitions are performed. Subsequently, three trial repetitions are performed, each with 60 seconds of rest in between. The greatest peak and mean power output in watts (W) of the three trial repetitions are used for analysis.	Baseline
Secondary	Muscle Power	Muscular power will be assessed using a linear position transducer (LPT). A sit-to-stand (STS) power test will be performed. Two practice repetitions are performed. Subsequently, three trial repetitions are performed, each with 60 seconds of rest in between. The greatest peak and mean power output in watts (W) of the three trial repetitions are used for analysis.	12 weeks
Secondary	Muscle Power	Muscular power will be assessed using a linear position transducer (LPT). A sit-to-stand (STS) power test will be performed. Two practice repetitions are performed. Subsequently, three trial repetitions are performed, each with 60 seconds of rest in between. The greatest peak and mean power output in watts (W) of the three trial repetitions are used for analysis.	24 weeks
Secondary	Fatigue: FACIT-F	Fatigue will be measured using the Functional Assessment of Chronic Illness Therapy Fatigue, a 1-page form that uses a rating scale that goes from 0 (no fatigue) to 10 (severe fatigue). It assesses the patient's fatigue levels in the last 7 days. It also measures how usual activities, performing work, walking, relationship, and enjoyment of life are affected by fatigue. A higher score indicates higher levels of perceived fatigue. Clinically meaningful changes are 3 points.	Baseline
Secondary	Fatigue: FACIT-F	Fatigue will be measured using the Functional Assessment of Chronic Illness Therapy Fatigue, a 1-page form that uses a rating scale that goes from 0 (no fatigue) to 10 (severe fatigue). It assesses the patient's fatigue levels in the last 7 days. It also measures how usual activities, performing work, walking, relationship, and enjoyment of life are affected by fatigue. A higher score indicates higher levels of perceived fatigue. Clinically meaningful changes are 3 points.	12 weeks
Secondary	Fatigue: FACIT-F	Fatigue will be measured using the Functional Assessment of Chronic Illness Therapy Fatigue, a 1-page form that uses a rating scale that goes from 0 (no fatigue) to 10 (severe fatigue). It assesses the patient's fatigue levels in the last 7 days. It also measures how usual activities, performing work, walking, relationship, and enjoyment of life are affected by fatigue. A higher score indicates higher levels of perceived fatigue. Clinically meaningful changes are 3 points.	24 weeks
Secondary	Depression and Anxiety	Depression will be measured using the Hospital Anxiety and Depression Scale (HADS), a concise, self-administered 1 page form that categorizes anxiety and depression. The total score goes from 0-21, and scores are categorized from minimal to severe depression/anxiety, with higher total scores indicate worse outcomes.	Baseline
Secondary	Depression and Anxiety	Depression will be measured using the Hospital Anxiety and Depression Scale (HADS), a concise, self-administered 1 page form that categorizes anxiety and depression. The total score goes from 0-21, and scores are categorized from minimal to severe depression/anxiety, with higher total scores indicate worse outcomes.	12 weeks
Secondary	Depression and Anxiety	Depression will be measured using the Hospital Anxiety and Depression Scale (HADS), a concise, self-administered 1 page form that categorizes anxiety and depression. The total score goes from 0-21, and scores are categorized from minimal to severe depression/anxiety, with higher total scores indicate worse outcomes.	24 weeks
Secondary	Bone Pain: FACT-BP	Bone pain will be determined using the FACT-BP questionnaire. FACT-BP is a 15-item scale assessing cancer-related bone pain and its effects on quality of life (QoL); the higher the aggregate score, the less the bone pain and/or the better the QoL. All scales score from 0-4 and a high scale score represents a higher response level. Minimal important differences for FACT-BP range from 3-7 points.	Baseline
Secondary	Bone Pain: FACT-BP	Bone pain will be determined using the FACT-BP questionnaire. FACT-BP is a 15-item scale assessing cancer-related bone pain and its effects on quality of life (QoL); the higher the aggregate score, the less the bone pain and/or the better the QoL. All scales score from 0-4 and a high scale score represents a higher response level. Minimal important differences for FACT-BP range from 3-7 points.	12 weeks
Secondary	Bone Pain: FACT-BP	Bone pain will be determined using the FACT-BP questionnaire. FACT-BP is a 15-item scale assessing cancer-related bone pain and its effects on quality of life (QoL); the higher the aggregate score, the less the bone pain and/or the better the QoL. All scales score from 0-4 and a high scale score represents a higher response level. Minimal important differences for FACT-BP range from 3-7 points.	24 weeks
Secondary	Quality of Life: FACT-P	Quality of life (QoL) will be measured using the Functional Assessment of Cancer Therapy-Prostate (FACT-P). The FACT-P is composed of both multi-item scales and single-item measures. These include physical, social, emotional, and functional well-being, along with an assessment of prostate-specific health status. five functional scales, three symptom scales, a global health status / QoL scale, and six single items. All scales score from 0-4 and a higher score represents higher QoL. Clinically meaningful changes are 6-10 points.	Baseline
Secondary	Quality of Life: FACT-P	Quality of life (QoL) will be measured using the Functional Assessment of Cancer Therapy-Prostate (FACT-P). The FACT-P is composed of both multi-item scales and single-item measures. These include physical, social, emotional, and functional well-being, along with an assessment of prostate-specific health status. five functional scales, three symptom scales, a global health status / QoL scale, and six single items. All scales score from 0-4 and a higher score represents higher QoL. Clinically meaningful changes are 6-10 points.	12 weeks
Secondary	Quality of Life: FACT-P	Quality of life (QoL) will be measured using the Functional Assessment of Cancer Therapy-Prostate (FACT-P). The FACT-P is composed of both multi-item scales and single-item measures. These include physical, social, emotional, and functional well-being, along with an assessment of prostate-specific health status. five functional scales, three symptom scales, a global health status / QoL scale, and six single items. All scales score from 0-4 and a higher score represents higher QoL. Clinically meaningful changes are 6-10 points.	24 weeks
Secondary	Balance: NeuroCom	Balance will be assessed using the NeuroCom Smart Balance Master. A sensory organization test will be performed. An overall composite equilibrium score describing a person's overall level of performance during all of the trials in the sensory organization test is calculated, with a value between 0 and 100, with 0 indicating a large sway and loss of balance, and 100 indicating greater postural control. The composite score is a weighted-average of the following 14 scores: the condition 1 average score, the condition 2 average score, and the three equilibrium scores from each of the trials in conditions 3-6.	Baseline
Secondary	Balance: NeuroCom	Balance will be assessed using the NeuroCom Smart Balance Master. A sensory organization test will be performed. An overall composite equilibrium score describing a person's overall level of performance during all of the trials in the sensory organization test is calculated, with a value between 0 and 100, with 0 indicating a large sway and loss of balance, and 100 indicating greater postural control. The composite score is a weighted-average of the following 14 scores: the condition 1 average score, the condition 2 average score, and the three equilibrium scores from each of the trials in conditions 3-6.	12 weeks
Secondary	Balance: NeuroCom	Balance will be assessed using the NeuroCom Smart Balance Master. A sensory organization test will be performed. An overall composite equilibrium score describing a person's overall level of performance during all of the trials in the sensory organization test is calculated, with a value between 0 and 100, with 0 indicating a large sway and loss of balance, and 100 indicating greater postural control. The composite score is a weighted-average of the following 14 scores: the condition 1 average score, the condition 2 average score, and the three equilibrium scores from each of the trials in conditions 3-6.	24 weeks
Secondary	Arterial Stiffness: SphygmoCor	Arterial stiffness will be measured using the SphygmoCor Xcel (AtCor Medical). Arterial stiffness will be assessed using brachial pulse wave analysis (PWA) augmentation index and carotid-femoral pulse wave analysis (PWV). Greater PWA augmentation index and carotid-femoral PWV time indicates greater arterial stiffness, a surrogate end-point for cardiovascular disease.	Baseline
Secondary	Arterial Stiffness: SphygmoCor	Arterial stiffness will be measured using the SphygmoCor Xcel (AtCor Medical). Arterial stiffness will be assessed using brachial pulse wave analysis (PWA) augmentation index and carotid-femoral pulse wave analysis (PWV). Greater PWA augmentation index and carotid-femoral PWV time indicates greater arterial stiffness, a surrogate end-point for cardiovascular disease.	12 weeks
Secondary	Arterial Stiffness: SphygmoCor	Arterial stiffness will be measured using the SphygmoCor Xcel (AtCor Medical). Arterial stiffness will be assessed using brachial pulse wave analysis (PWA) augmentation index and carotid-femoral pulse wave analysis (PWV). Greater PWA augmentation index and carotid-femoral PWV time indicates greater arterial stiffness, a surrogate end-point for cardiovascular disease.	24 weeks