Strength and Muscle Related Outcomes for Nutrition and Lung Function in CF

Study Overview
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Brief Summary
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The goal of the study is to examine multiple markers of anthropometrics, body composition, sarcopenia and frailty and compare them to dual energy X-ray absorptiometry (DXA) output, which is considered the current clinical gold-standard tool to measure body composition. The result of this study will provide detailed data regarding the nutrition and body composition within this Cystic Fibrosis population and also provide a baseline evaluation for use of these biomarkers in the future studies including evaluation of nutritional intervention. Further, the study will also include psychosocial and other patient-reported outcomes and medical contributors to understand their contributions to the nutritional failure in the adult advanced lung disease population. Finally, the study will evaluate both established and emerging nutritional and body composition parameters and link them to clinical outcomes in adults with CF across the spectrum of pulmonary function.

Official Title
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Strength and Muscle Related Outcomes for Nutrition and Lung Function in CF

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Diagnostic Test: BMI and lean mass index from DXA
* Diagnostic Test: skinfold and circumference
* Diagnostic Test: Hand-grip strength
* Diagnostic Test: 6-minute walk
* Diagnostic Test: 1-minute site to stand
* Diagnostic Test: Short physical performance battery (SPPB)
* Diagnostic Test: BIA Sub-study
* Diagnostic Test: Accelerometry to assess physical activity
* Other: Gastrointestinal (GI) and nutrition questionnaires
* Other: Psychosocial questionnaire: PHQ-8
* Other: Psychosocial questionnaire: GAD-7
* Other: Psychosocial questionnaire: The Treatment Self-Regulation Questionnaire (TSRQ)
* Other: Psychosocial questionnaire: CF Fatalism Scale
* Other: Psychosocial questionnaire: Body Esteem Scale for Adolescents and Adults (BESAA)
* Other: STRONG Participant Experience Survey
* Other: Oral glucose tolerance testing (OGTT)
* Device: Continuous glucose monitoring (CGM)
* Diagnostic Test: Chest CT scans (When available within the past 6 months in medical records)
* Diagnostic Test: Hologic Dual X-Ray Absorptiometry (DXA)
* Diagnostic Test: Ultrasound Sub-study of assessment of appendage muscles using ultrasound
* Diagnostic Test: Hunger Vital Sign questionnaire
* Other: Respiratory symptom questionnaire: CRISS
* Diagnostic Test: Spirometry
* Other: Food logging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cohort 1: Patients are eligible if their percentage of predicated forced expiratory volume in1 second (FEV1) is 60% or lower at screening. Cohort 2: Patients are eligible if their percentage of predicted forced expiratory volume in 1 second (FEV1) is 60% or greater at screening. Both cohorts match by age, gender, race and CFTR genotype severity. Exclusion Criteria: No prior solid organ transplantation No initiation of an investigation drug within 28 days prior to and including Visit 1 No initiation of new chronic therapy (e.g., ibuprofen, azithromycin, inhaled tobramycin, Cayston, CFTR modulator) within 28 days prior to and including Visit 1. No acute use of antibiotics (oral, inhaled or IV) or acute use of systemic corticosteroids for respiratory tract sympoms within 14 days prior to and including Visit 1. For the BIA sub-study - Individuals with an implanted pacemaker will be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1<br>Forced expiratory volume in 1 second (FEV1) <60% predicted during the 12 months prior to enrollment (>50% of measurements, eliminating periods of exacerbation). If no stable spirometry data are available in the 12 months prior to enrollment, from the prior 24 months will be used. | Diagnostic Test: BMI and lean mass index from DXA<br>* Estimate and compare correlation between lean mass index from DXA and BMI<br>Diagnostic Test: skinfold and circumference<br>* Skinfold will be assessed with calipers. Circumference will be measured with a tape measure.<br>Diagnostic Test: Hand-grip strength<br>* A small, handheld dynamometer will be used to measure grip strength, a measure of function, on each hand.<br>Diagnostic Test: 6-minute walk<br>* This will be another functional assessment of fitness. Participants will be asked to walk at their normal pace for 6 minutes.<br>Diagnostic Test: 1-minute site to stand<br>* This will be used as a functional assessment of fitness and lower extremity strength. Participants will start seated on a chair and be asked to complete as many sit-to-stand repetitions without using their arms for one minute.<br>Diagnostic Test: Short physical performance battery (SPPB)<br>* This is an assessment of frailty. The test is completed in approximately 8 minutes. The test consists of 3 assessments: 1) Balance tests where the participant stands and tries to balance with their feet in various positions for 10 seconds each without assistance (side-by-side, heel-to-side, and heel-to-toe); 2) Two 4-meter gait speed tests; and 3) Chair-stand tests (single chair stand, 5 chair stands).<br>Diagnostic Test: BIA Sub-study<br>* A minimum of 50 individuals will be enrolled. Body composition will be assessed at each study visit using study bioelectrical impendence analysis (BIA).<br>Diagnostic Test: Accelerometry to assess physical activity<br>* Participants will be provided with a wrist-worn accelerometer/heart rate monitor at the baseline study visit and asked to wear it continuously for at least 3-10 days (at least two weekdays, one weekend day). Approximately every 3 months, the participant will be asked to again wear the accelerometer. Participants will be able to keep their accelerometers.<br>Other: Gastrointestinal (GI) and nutrition questionnaires<br>* Subjects will complete surveys regarding gastrointestinal (GI) symptoms, including the Patient Assessment of Constipation (PAC-SYM) Score, Patient Assessment of Gastrointestinal Symptoms (PACGI-SYM) Score, the Bristol Stool Chart, and the scored Patient-Generated Subjective Global Assessment (PG-SGA).<br>Other: Psychosocial questionnaire: PHQ-8<br>* This is an 8-item scale that measures depressive symptoms over the past two weeks.<br>Other: Psychosocial questionnaire: GAD-7<br>* This is a 7-items scale that measures anxiety symptoms over the past two weeks, from not at all to nearly every day.<br>Other: Psychosocial questionnaire: The Treatment Self-Regulation Questionnaire (TSRQ)<br>* This is a 15-item scale that assesses the degree to which participants' motivation is autonomous or self-regulated.<br>Other: Psychosocial questionnaire: CF Fatalism Scale<br>* The CF Fatalism Scale measures the belief in a lack of personal power or control over one's future and has 13 items.<br>Other: Psychosocial questionnaire: Body Esteem Scale for Adolescents and Adults (BESAA)<br>* The Body Esteem Scale for Adolescents and Adults (BESAA) is 23-item measurement of self-evaluations of one's body or appearance.<br>Other: STRONG Participant Experience Survey<br>* A short questionnaire designed to explore participants' perspectives of the acceptability and feasibility of nutritional assessments used in STRONG-CF will be given to all study participants at the end of the study.<br>Other: Oral glucose tolerance testing (OGTT)<br>* For subjects without previously diagnosed CFRD, an OGTT will be performed at baseline and 12-months with samples analyzed at the central lab.<br>Device: Continuous glucose monitoring (CGM)<br>* Subjects will wear a Dexcom G6Pro sensor in blinded mode for three 10-day periods to collect comprehensive glucose data.<br>Diagnostic Test: Chest CT scans (When available within the past 6 months in medical records)<br>* Standard of Care chest CT images will be drawn from the medical record, as available, from enrolled participants. FEV1 measurements prior to chest CT scans will be recorded to account for possible illness occurring at the time of scanning. Quantitative assessment of the pectoralis muscle area will be performed on the first single axial image above the aortic arch. Any additional standard of care chest CT's that are performed while the participant is enrolled in the study will also be collected and have a quantitative assessment of the pectoralis muscle performed.<br>Diagnostic Test: Hologic Dual X-Ray Absorptiometry (DXA)<br>* DXA measurements for whole body, total hip and lumbar spine will be acquired using the Hologic DXA and standard positioning as noted in the DXA Manual of Operations. DXA will be used to estimate total and regional body composition, which will include body fat and lean body mass. This will be used as the gold standard from which to validate BIA and MAMC.<br>Diagnostic Test: Ultrasound Sub-study of assessment of appendage muscles using ultrasound<br>* A minimum of 50 individuals will be enrolled. At each study visit, participants will undergo ultrasound muscle measurements (cross-sectional area and muscle thickness) of the biceps and quadriceps on each (left and right) side of the body (4 total areas). These measurements will be obtained in triplicate for each patient.<br>Diagnostic Test: Hunger Vital Sign questionnaire<br>* Screening tool for identifying households at risk of food insecurity and poor health outcomes linked to food insecurity with 3-items over the last 12 months.<br>Other: Respiratory symptom questionnaire: CRISS<br>* Chronic Respiratory Infection Symptom Score (CRISS) is an 8-item respiratory symptom questionnaire covering the last 24-hours.<br>Diagnostic Test: Spirometry<br>* Spirometry will be performed in accordance with the current American Thoracic Society recommendations for the performance and interpretation of tests.<br>Other: Food logging<br>* Subjects will be requested to complete an electronic food diary for at least 3 days and a maximum of 10 days (2 weekdays, 1 weekend day) to document dietary intake pre-specified days during the study period.<br>|
| Cohort 2<br>FEV1 ≥60% predicted during the 12 months prior to enrollment (>50% of measurements, eliminating periods of exacerbation). | Diagnostic Test: BMI and lean mass index from DXA<br>* Estimate and compare correlation between lean mass index from DXA and BMI<br>Diagnostic Test: skinfold and circumference<br>* Skinfold will be assessed with calipers. Circumference will be measured with a tape measure.<br>Diagnostic Test: Hand-grip strength<br>* A small, handheld dynamometer will be used to measure grip strength, a measure of function, on each hand.<br>Diagnostic Test: 6-minute walk<br>* This will be another functional assessment of fitness. Participants will be asked to walk at their normal pace for 6 minutes.<br>Diagnostic Test: 1-minute site to stand<br>* This will be used as a functional assessment of fitness and lower extremity strength. Participants will start seated on a chair and be asked to complete as many sit-to-stand repetitions without using their arms for one minute.<br>Diagnostic Test: Short physical performance battery (SPPB)<br>* This is an assessment of frailty. The test is completed in approximately 8 minutes. The test consists of 3 assessments: 1) Balance tests where the participant stands and tries to balance with their feet in various positions for 10 seconds each without assistance (side-by-side, heel-to-side, and heel-to-toe); 2) Two 4-meter gait speed tests; and 3) Chair-stand tests (single chair stand, 5 chair stands).<br>Diagnostic Test: BIA Sub-study<br>* A minimum of 50 individuals will be enrolled. Body composition will be assessed at each study visit using study bioelectrical impendence analysis (BIA).<br>Diagnostic Test: Accelerometry to assess physical activity<br>* Participants will be provided with a wrist-worn accelerometer/heart rate monitor at the baseline study visit and asked to wear it continuously for at least 3-10 days (at least two weekdays, one weekend day). Approximately every 3 months, the participant will be asked to again wear the accelerometer. Participants will be able to keep their accelerometers.<br>Other: Gastrointestinal (GI) and nutrition questionnaires<br>* Subjects will complete surveys regarding gastrointestinal (GI) symptoms, including the Patient Assessment of Constipation (PAC-SYM) Score, Patient Assessment of Gastrointestinal Symptoms (PACGI-SYM) Score, the Bristol Stool Chart, and the scored Patient-Generated Subjective Global Assessment (PG-SGA).<br>Other: Psychosocial questionnaire: PHQ-8<br>* This is an 8-item scale that measures depressive symptoms over the past two weeks.<br>Other: Psychosocial questionnaire: GAD-7<br>* This is a 7-items scale that measures anxiety symptoms over the past two weeks, from not at all to nearly every day.<br>Other: Psychosocial questionnaire: The Treatment Self-Regulation Questionnaire (TSRQ)<br>* This is a 15-item scale that assesses the degree to which participants' motivation is autonomous or self-regulated.<br>Other: Psychosocial questionnaire: CF Fatalism Scale<br>* The CF Fatalism Scale measures the belief in a lack of personal power or control over one's future and has 13 items.<br>Other: Psychosocial questionnaire: Body Esteem Scale for Adolescents and Adults (BESAA)<br>* The Body Esteem Scale for Adolescents and Adults (BESAA) is 23-item measurement of self-evaluations of one's body or appearance.<br>Other: STRONG Participant Experience Survey<br>* A short questionnaire designed to explore participants' perspectives of the acceptability and feasibility of nutritional assessments used in STRONG-CF will be given to all study participants at the end of the study.<br>Other: Oral glucose tolerance testing (OGTT)<br>* For subjects without previously diagnosed CFRD, an OGTT will be performed at baseline and 12-months with samples analyzed at the central lab.<br>Device: Continuous glucose monitoring (CGM)<br>* Subjects will wear a Dexcom G6Pro sensor in blinded mode for three 10-day periods to collect comprehensive glucose data.<br>Diagnostic Test: Chest CT scans (When available within the past 6 months in medical records)<br>* Standard of Care chest CT images will be drawn from the medical record, as available, from enrolled participants. FEV1 measurements prior to chest CT scans will be recorded to account for possible illness occurring at the time of scanning. Quantitative assessment of the pectoralis muscle area will be performed on the first single axial image above the aortic arch. Any additional standard of care chest CT's that are performed while the participant is enrolled in the study will also be collected and have a quantitative assessment of the pectoralis muscle performed.<br>Diagnostic Test: Hologic Dual X-Ray Absorptiometry (DXA)<br>* DXA measurements for whole body, total hip and lumbar spine will be acquired using the Hologic DXA and standard positioning as noted in the DXA Manual of Operations. DXA will be used to estimate total and regional body composition, which will include body fat and lean body mass. This will be used as the gold standard from which to validate BIA and MAMC.<br>Diagnostic Test: Ultrasound Sub-study of assessment of appendage muscles using ultrasound<br>* A minimum of 50 individuals will be enrolled. At each study visit, participants will undergo ultrasound muscle measurements (cross-sectional area and muscle thickness) of the biceps and quadriceps on each (left and right) side of the body (4 total areas). These measurements will be obtained in triplicate for each patient.<br>Diagnostic Test: Hunger Vital Sign questionnaire<br>* Screening tool for identifying households at risk of food insecurity and poor health outcomes linked to food insecurity with 3-items over the last 12 months.<br>Other: Respiratory symptom questionnaire: CRISS<br>* Chronic Respiratory Infection Symptom Score (CRISS) is an 8-item respiratory symptom questionnaire covering the last 24-hours.<br>Diagnostic Test: Spirometry<br>* Spirometry will be performed in accordance with the current American Thoracic Society recommendations for the performance and interpretation of tests.<br>Other: Food logging<br>* Subjects will be requested to complete an electronic food diary for at least 3 days and a maximum of 10 days (2 weekdays, 1 weekend day) to document dietary intake pre-specified days during the study period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between DXA lean mass index and BMI | Estimate and compare correlation between lean mass index from DXA (kg/m2) and BMI (kg/m2) | Baseline and 1 year | 
| Correlation between DXA lean mass index and mid-arm muscle circumference | Estimate and compare correlation between lean mass index from DXA (kg/m2) and mid-arm muscle circumference (cm) | Baseline and 1 year | 
| Correlation between DXA lean mass index and hand-grip strength | Estimate and compare correlation between lean mass index from DXA (kg/m2) and hand-grip strength (kg) | Baseline and 1 year | 
| Correlation between DXA lean mass index and the 6-minute walk distance traveled | Estimate and compare correlation between lean mass index from DXA (kg/m2) and 6-minute walk (distance traveled in six minutes) | Baseline and 1 year | 
| Correlation between DXA lean mass index and the 1-minute sit-to-stand number of repetitions | Estimate and compare correlation between lean mass index from DXA (kg/m2) and 1-minute sit-to-stand (number of sit-to-stand repetitions in one minute) | Baseline and 1 year | 
| Correlation between DXA lean mass index and Short Physical Performance Battery frailty score | Estimate and compare correlation between lean mass index from DXA (kg/m2) and Short Physical Performance Battery frailty score (total points) | Baseline and 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize lean mass index from DXA cross-sectionally and longitudinally | Characterize lean mass index from DXA cross-sectionally (at enrollment) and longitudinally (post-enrollment changes) based on descriptive statistics and evaluate variance | Baseline and 1 year | 
| Characterize BMI cross-sectionally and longitudinally | Characterize lean mass index from BMI cross-sectionally (at enrollment) and longitudinally (post-enrollment changes) based on descriptive statistics and evaluate variance | Baseline and 1 year | 
| Characterize mid-arm measurement circumference cross-sectionally and longitudinally | Characterize lean mass index from mid-arm circumference measurements cross-sectionally (at enrollment) and longitudinally (post-enrollment changes) based on descriptive statistics and evaluate variance | Baseline and 1 year | 
| Characterize hand-grip strength cross-sectionally and longitudinally | Characterize hand-grip strength cross-sectionally (at enrollment) and longitudinally (post-enrollment changes) based on descriptive statistics and evaluate variance | Baseline and 1 year | 
| Characterize 1 minute sit-to-stand repetitions cross-sectionally and longitudinally | Characterize the 1 minute sit-to-stand repetitions cross-sectionally (at enrollment) and longitudinally (post-enrollment changes) based on descriptive statistics and evaluate variance | Baseline and 1 year | 
| Characterize mid-arm 6-minute walk test distance traveled cross-sectionally and longitudinally | Characterize the 6-minute walk test distance traveled cross-sectionally (at enrollment) and longitudinally (post-enrollment changes) based on descriptive statistics and evaluate variance | Baseline and 1 year | 
| Characterize the Short Physical Performance Battery frailty score cross-sectionally and longitudinally | Characterize the Short Physical Performance Battery frailty score cross-sectionally (at enrollment) and longitudinally (post-enrollment changes) based on descriptive statistics and evaluate variance | Baseline and 1 year | 
| Compare lean mass index from DXA between participants with FEV1 <60% to matched participants with FEV1 ≥60% | Compare lean mass index from DXA between participants with FEV1 <60% to matched participants with FEV1 ≥60%. | Baseline and 1 year | 
| Compare BMI between participants with FEV1 <60% to matched participants with FEV1 ≥60% | Compare BMI between participants with FEV1 <60% to matched participants with FEV1 ≥60%. | Baseline and 1 year | 
| Compare lean mass index from mid-arm muscle circumference between participants with FEV1 <60% to matched participants with FEV1 ≥60% | Compare lean mass index from mid-arm muscle circumference between participants with FEV1 <60% to matched participants with FEV1 ≥60%. | Baseline and 1 year | 
| Compare hand-grip strength between participants with FEV1 <60% to matched participants with FEV1 ≥60% | Compare hand-grip strength between participants with FEV1 <60% to matched participants with FEV1 ≥60%. | Baseline and 1 year | 
| Compare the 1-minute sit-to-stand repetitions between participants with FEV1 <60% to matched participants with FEV1 ≥60% | Compare the 1-minute sit-to-stand repetitions between participants with FEV1 <60% to matched participants with FEV1 ≥60%. | Baseline and 1 year | 
| Compare the 6-minute walk test distance between participants with FEV1 <60% to matched participants with FEV1 ≥60% | Compare the 6-minute walk test distance between participants with FEV1 <60% to matched participants with FEV1 ≥60%. | Baseline and 1 year | 
| Compare the Short Physical Performance Battery frailty score between participants with FEV1 <60% to matched participants with FEV1 ≥60% | Compare the Short Physical Performance Battery frailty score between participants with FEV1 <60% to matched participants with FEV1 ≥60%. | Baseline and 1 year | 
| Evaluate mean glucose in participants with FEV1 <60% and matched participants with FEV1 ≥60% | Evaluate mean glucose from continuous glucose measurement data in participants with FEV1 <60% and matched participants with FEV1 ≥60% | Baseline and 1 year | 
| Evaluate % time above 140 mg/dL in participants with FEV1 <60% and matched participants with FEV1 ≥60% | Evaluate % time above 140 mg/dL from continuous glucose measurement data in participants with FEV1 <60% and matched participants with FEV1 ≥60% | Baseline and 1 year | 
| Evaluate % time above 180 mg/dL in participants with FEV1 <60% and matched participants with FEV1 ≥60% | Evaluate % time above 180 mg/dL from continuous glucose measurement data in participants with FEV1 <60% and matched participants with FEV1 ≥60% | Baseline and 1 year | 
| Evaluate peak glucose in participants with FEV1 <60% and matched participants with FEV1 ≥60% | Evaluate peak glucose from continuous glucose measurement data in participants with FEV1 <60% and matched participants with FEV1 ≥60% | Baseline and 1 year | 
| Evaluate % time below 70 mg/dL in participants with FEV1 <60% and matched participants with FEV1 ≥60% | Evaluate % time below 70 mg/dL from continuous glucose measurement data in participants with FEV1 <60% and matched participants with FEV1 ≥60% | Baseline and 1 year | 
| Evaluate % time below 54 mg/dL in participants with FEV1 <60% and matched participants with FEV1 ≥60% | Evaluate % time below 54 mg/dL from continuous glucose measurement data in participants with FEV1 <60% and matched participants with FEV1 ≥60% | Baseline and 1 year | 
| Evaluate the standard deviation in CGM glucose data in participants with FEV1 <60% and matched participants with FEV1 ≥60% | Evaluate the standard deviation in CGM glucose data in participants with FEV1 <60% and matched participants with FEV1 ≥60% | Baseline and 1 year | 
| Evaluate the coefficient of variation in CGM glucose data in participants with FEV1 <60% and matched participants with FEV1 ≥60%participants with FEV1 ≥60% | Evaluate the coefficient of variation in CGM glucose data in participants with FEV1 <60% and matched participants with FEV1 ≥60%participants with FEV1 ≥60% | Baseline and 1 year |