Incorporating Nutrition, Vests, Education, and Strength Training in Bone Health (INVEST in Bone Health) (INVEST)

• ClinicalTrials.gov Identifier: NCT04076618
• Recruitment Status: Active, not recruiting
• First Posted: September 3, 2019
• Last Update Posted: March 6, 2023
• Sponsor: Wake Forest University Health Sciences
• Information provided by (Responsible Party): Wake Forest University Health Sciences

Study Description

Brief Summary:

The main goal of the proposed study is to compare the effects of weight loss (WL) alone with WL plus weighted vest use or WL plus resistance exercise training (RT) on indicators of bone health and subsequent fracture risk.

Condition or disease	Intervention/treatment	Phase
Weight Loss; Bone Health	Device: Vest; Behavioral: Resistance Exercise Training; Behavioral: weight loss program	Not Applicable

Detailed Description:

The study team proposes that a 12 month trial in 150 older (60-85 years) adults with obesity (Body mass index or BMI=30-40 kg/m2 OR 27.0-<30 kg/m² and one obesity-related risk factor) randomized to one of three interventions (n=64/group): WL alone (WL; caloric restriction targeting 10% WL); WL plus weighted vest use (WL+Vest); targeting ≥8 hours/day, weight replacement titrated up to 10% WL); or, WL plus structured RT (WL+RT; 3 days/week). Total hip trabecular volumetric bone mineral density (vBMD) is the primary outcome. This outcome will be complemented by exploratory assessment of several fracture-related risk factors, including: (1) femoral neck and lumbar spine vBMD, cortical thickness, finite element modeling of bone strength, and regional fat and muscle volumes, measured by CT; (2) areal bone mineral density (aBMD) at the total hip, femoral neck, lumbar spine, and distal radius; trabecular bone score; and total body fat/lean masses, measured by dual energy x-ray absorptiometry (DXA); (3) muscle function and strength; (4) biomarkers of bone turnover; and (5) bone-regulating hormones/cytokines known to influence bone metabolism during WL. Therefore, the investigators Specific Aims are to:

Aim 1: Determine the effects of WL+VEST compared to WL and WL+RT on 12 month change in total hip trabecular vBMD. Despite similar reductions in total body weight, Hypothesis 1: Participants in the WL+VEST group will show attenuated losses of total hip trabecular vBMD versus WL; and Hypothesis 2: Loss in total hip trabecular vBMD will be no greater in WL+VEST compared to WL+RT.

Aim 2: Explore the effects of WL+VEST compared to WL and WL+RT on the 12 month change in fracture-related risk factors. Despite similar reductions in total body weight, we hypothesize that WL+VEST and WL+RT will demonstrate improvements in fracture-related risk factors compared to WL.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Incorporating Nutrition, Vests, Education, and Strength Training in Bone Health (INVEST in Bone Health)
• Actual Study Start Date: August 12, 2020
• Estimated Primary Completion Date: March 31, 2024
• Estimated Study Completion Date: March 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Weight Loss plus Vest	Device: Vest; Weighted Vest worn > or = 8 hours per day; Behavioral: weight loss program; a 24-week intensive phase (with weekly dietary classes) followed by a 27-week transition phase (with biweekly dietary classes)
Active Comparator: Weight Loss Plus Resistance Exercise Training	Behavioral: Resistance Exercise Training; Structured exercise training 3 days a week; Behavioral: weight loss program; a 24-week intensive phase (with weekly dietary classes) followed by a 27-week transition phase (with biweekly dietary classes)
Active Comparator: Weight Loss	Behavioral: weight loss program; a 24-week intensive phase (with weekly dietary classes) followed by a 27-week transition phase (with biweekly dietary classes)

Outcome Measures

Primary Outcome Measures :

1. Change in total hip trabecular volumetric bone mineral density (vBMD) [ Time Frame: 12 months from baseline ]
   measured in mg/cm3 during computed tomography (CT) scan

Secondary Outcome Measures :

1. Change in total hip trabecular volumetric bone mineral density (vBMD) [ Time Frame: 6 months from baseline ]
   measured in mg/cm3 during computed tomography (CT) scan
2. Change in femoral neck volumetric bone mineral density (vBMD) [ Time Frame: 12 months from baseline ]
   measured in mg/cm3 during computed tomography (CT) scan
3. Change in lumbar spine volumetric bone mineral density (vBMD) [ Time Frame: 12 months from baseline ]
   measured in mg/cm3 during computed tomography (CT) scan
4. Trabecular bone score (TBS) [ Time Frame: 12 months from baseline ]
   measurement taken during dual energy x-ray absorptiometry (DXA) scan; Trabecular Bone Score is a measure of bone architecture that has been shown to be an independent risk factor for fracture. The measure is unitless, and ranges from 1.0-1.6, where an elevated TBS greater than or equal to 1.3 appears to represent strong, fracture-resistant bone architecture, while a low TBS less than or equal to 1.2 reflects weak, fracture-prone bone architecture.
5. Change in total hip areal bone mineral density (aBMD) [ Time Frame: 12 months from baseline ]
   measured in g/cm2 during dual energy x-ray absorptiometry (DXA) scan
6. Change in femoral neck areal bone mineral density (aBMD) [ Time Frame: 12 months from baseline ]
   measured in g/cm2 during dual energy x-ray absorptiometry (DXA) scan
7. Change in distal radius areal bone mineral density (aBMD) [ Time Frame: 12 months from baseline ]
   measured in g/cm2 during dual energy x-ray absorptiometry (DXA) scan
8. Change in lumbar spine areal bone mineral density (aBMD) [ Time Frame: 12 months from baseline ]
   measured in g/cm2 during dual energy x-ray absorptiometry (DXA) scan
9. Change in total body fat mass (kg) [ Time Frame: 12 months from baseline ]
   measurement taken during dual energy x-ray absorptiometry (DXA) scan
10. Change in total body lean mass (kg) [ Time Frame: 12 months from baseline ]
    measurement taken during dual energy x-ray absorptiometry (DXA)

Other Outcome Measures:

1. Mid-thigh muscle density measured in HU [ Time Frame: 12 months from baseline ]
   measurement taken during computed tomography (CT) scan
2. Intermuscular fat CSA (cm2) [ Time Frame: 12 months from baseline ]
   measurement taken during computed tomography (CT) scan
3. Cortical thickness (mm) [ Time Frame: 12 months from baseline ]
   measurement taken during computed tomography (CT) scan
4. Finite element (FE) modeling of bone strength measured in kN [ Time Frame: 12 months from baseline ]
   measurement taken during computed tomography (CT) scan
5. Mid-thigh muscle volume measured in cm3 [ Time Frame: 12 months from baseline ]
   measurement taken during computed tomography (CT) scan
6. Mid-thigh intermuscular fat measured in cm3 [ Time Frame: 12 months from baseline ]
   measurement taken during computed tomography (CT) scan
7. P1NP (ug/L) [ Time Frame: 12 months from baseline ]
   Biomarkers of bone turnover measured via blood specimen
8. CTX (pg/mL) [ Time Frame: 12 months from baseline ]
   Biomarkers of bone turnover measured via blood specimen
9. D3-Creatine derived muscle mass measured in kg [ Time Frame: 12 months from baseline ]
   measurement taken via urine sample
10. Gait speed [ Time Frame: 12 months from baseline ]
    measured in m/s during the 400 meter walk test
11. expanded Short Physical Performance Battery (eSPPB) [ Time Frame: 12 months from baseline ]
    The SPPB is a measure of balance, walking speed, and ability to stand from a chair. It provides a global measure of overall physical function and is a good predictor of future disability, institutionalization, and mortality in older persons. The SPPB score is calculated by assigning each of the test measures (balance, walking speed, and chair stands) a score from 0 (unable to do) to 4 (best) and then adding these scores together for a total score ranging from 0 to 12. An SPPB score less than 10 identifies persons at higher risk for mobility disability.
12. Timed-Up-and-Go (TUG) [ Time Frame: 12 months from baseline ]
    measured in seconds to assess physical performance; measures the time the participant takes to stand up from a standard chair, walk 3 meters, turn, walk back to the chair, and sit down again.
13. Stair climbing time [ Time Frame: 12 months from baseline ]
    measured in seconds using the participant's fastest time achieved to climb a 12 step staircase in two trials.
14. Lower extremity muscle strength [ Time Frame: 12 months from baseline ]
    measured using an isokinetic dynamometer with the participant sitting and the hips and knee flexed at 90°. Participants will be asked to extend the knee and push as hard as possible against the resistance pad. Strength is expressed as peak torque (Nm)
15. Grip strength [ Time Frame: 12 months from baseline ]
    measured twice in each hand to the nearest two kg using an isometric Jamar Hydraulic Hand Dynamometer with the mean value from the stronger hand used
16. Cognitive Assessment [ Time Frame: 12 months from baseline ]
    measured using the Montreal Cognitive Assessment (MOCA) with scores ranging from 0-30, with a score of 26 and higher generally considered normal.
17. Fatigability [ Time Frame: 12 months from baseline ]
    measured using the Pittsburgh Fatigability scale, which is a 10-item questionnaire that assesses fatigability, or the rate at which a person experiences mental or physical fatigue in the context of a standardized task. The scale ranges from 0-5, where those who exhibit more fatigability, score of 5, are more likely to limit activities of daily living and to reduce exertion during physical activities.
18. Pain and Fatigue [ Time Frame: 12 months from baseline ]
    measured using The Patient-Reported Outcomes Measurement Information System (PROMIS) instrument is an 8-item short-form that assesses pain and fatigue over the past 7 days. The scale ranges from 1-5, with higher scores indicated the presence of pain and fatigue.
19. Physical activity among older adults [ Time Frame: 12 months from baseline ]
    The CHAMPS questionnaire is a 40-43-item tool that assesses weekly frequency and duration of a variety of lifestyle physical activities that are appropriate for older adults. The purpose of this questionnaire is to evaluate the effectiveness of interventions to increase lifestyle physical activity among older adults. Physical activities are given a METS score, ranging from 2.0-7.0, where activities with a METS score of 3.0 or higher, are considered moderate intensity.
20. Overall limb loading [ Time Frame: 6 months from baseline ]
    measured in Newtons via force-sensing insoles to assess overall limb loading and to determine if participants receive enough loading to prevent bone loss from resistance training and weighted vest use when compared to weight loss alone.
21. Overall satisfaction participating in the optional insole visits [ Time Frame: 6 months from baseline ]
    overall satisfaction measured by a scale from 1-5 with a higher score indicating greater satisfaction

Eligibility Criteria

• Ages Eligible for Study: 60 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age 60-85 years
• BMI=30-40 kg/m^2 or BMI 27.0-<30.0 kg/m^2 plus one risk factor
• Weight stability - no weight loss > 5% in past 6 months
• No contraindications for safe and optimal participation in exercise training/vest use.
• Approved for participation by Study Coordinator
• Willing to provide informed consent; agree to all study procedures and assessments; Able to provide own transit to assessment/intervention visits
• Willing to complete online/electronic study forms and participate in virtual group sessions, as needed.

Exclusion Criteria:

• Weight greater than 450 lbs
• Dependent on cane or walker: >2 falls (injurious on non-injurious) in past year
• Any contraindications for participation in voluntary weight loss
• Smoker (>1 cigarette/d or 4/wk within yr); Excessive alcohol use (>14 drinks/wk)
• Participation in regular resistance training and/or high intensity/high impact aerobic exercise for >60 mins per day on > 5 days/week for the past 6 months
• Evidence of cognitive impairment (MoCA<20)
• Osteoporosis (self-report and on prescription medication, T-score < or = -2.5 on total hip, femoral neck, lumbar spine or distal radius scan at screening visit, or FRAX 10-year risk scores >3% for hip fracture or >20% for major osteoporotic fracture (TBS adjusted FRAX is preferable if available)
• Self-reported prior spine, hip, wrist, or shoulder fracture after age 40 (except when caused by trauma or fall from height)
• Chronic back/shoulder/knee pain with current or past (within 1 year) prescription medication use for at least 3 months
• Severe, diagnosed arthritis (osteoarthritis, rheumatoid arthritis, or gout) with current or past (within 1 year) prescription medication use for at least 3 months
• Past (ever) or planned (next 12 months) back surgery
• Past (6 months prior) or planned (next 12 months) joint replacement surgery; or past (ever) unilateral or bilateral hip replacement surgery
• Past (ever) metal device or fixation in the hip, pelvis, or femur
• Uncontrolled hypertension (BP > 160/90 mmHg)
• Current or recent past (within 1 year) severe symptomatic heart disease, uncontrolled angina, stroke, chronic respiratory disease requiring oxygen, neurological or hematological disease requiring treatment for at least 3 months in past year
• Cancer requiring treatment in past year, except non-melanoma skin cancer
• Low Vitamin D (<20 ng/mL)
• Abnormal kidney or liver function (2x upper limits of normal)
• eGFR<45 mL/min/1.73m2,
• Anemia (Hb <13 g/dL in men/<12 g/dL in women)
• Uncontrolled diabetes (fasting glucose > 140 mg/dL)
• Regular use of: growth hormones, weight loss medications, oral steroids, insulin, or prescription osteoporosis medications in the past year
• No home computer, laptop or tablet with reliable home internet OR no smartphone (touch-screen enabled phone) with reliable unlimited mobile internet
• Involved in another behavioral/interventional research study, weight loss program, or undergoing physical therapy.
• Unable to tolerate diet, vest, or CT scan (claustrophobia)
• Judged unsuitable for the trial for any reason by clinic staff

Contacts and Locations

Locations

United States, North Carolina

Wake Forest University School of Medicine

Winston-Salem, North Carolina, United States, 27157

Sponsors and Collaborators

Wake Forest University Health Sciences

Investigators

• Principal Investigator: Kristen Beavers, PhD, MPH, RD; Wake Forest University Health Sciences

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Miller RM, Beavers DP, Cawthon PM, Crotts C, Fanning J, Gerosa J, Greene KA, Hsieh KL, Kiel J, Lawrence E, Lenchik L, Lynch SD, Nesbit BA, Nicklas BJ, Weaver AA, Beavers KM. Incorporating Nutrition, Vests, Education, and Strength Training (INVEST) in Bone Health: Trial Design and Methods. Contemp Clin Trials. 2021 May;104:106326. doi: 10.1016/j.cct.2021.106326. Epub 2021 Feb 22.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT04076618
• Other Study ID Numbers: IRB00058279
• First Posted: September 3, 2019
• Last Update Posted: March 6, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Wake Forest University Health Sciences:

nutrition; vest

Additional relevant MeSH terms:

Weight Loss; Body Weight Changes; Body Weight