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

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.

Study Overview

• Status: Completed
• Conditions: Weight Loss; Bone Health
• Intervention / Treatment: Device: Vest; Behavioral: weight loss program; Behavioral: Resistance Exercise Training

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=50/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 Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Erica Lawrence; Phone Number: 336-713-8531; Email: erlawren@wakehealth.edu

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University School of Medicine

Participation Criteria

Eligibility Criteria

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

Description

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 fracture risk assessment tool (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)
• estimated glomerular filtration rate (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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / 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: weight loss program; a 24-week intensive phase (with weekly dietary classes) followed by a 27-week transition phase (with biweekly dietary classes); Behavioral: Resistance Exercise Training; Structured exercise training 3 days a week
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in total hip trabecular volumetric bone mineral density (vBMD)	measured in mg/cm3 during computed tomography (CT) scan	12 months from baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in total hip trabecular volumetric bone mineral density (vBMD)	measured in mg/cm3 during computed tomography (CT) scan	6 months from baseline
Change in femoral neck volumetric bone mineral density (vBMD)	measured in mg/cm3 during computed tomography (CT) scan	12 months from baseline
Change in lumbar spine volumetric bone mineral density (vBMD)	measured in mg/cm3 during computed tomography (CT) scan	12 months from baseline
Trabecular bone score (TBS)	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.	12 months from baseline
Change in total hip areal bone mineral density (aBMD)	measured in g/cm2 during dual energy x-ray absorptiometry (DXA) scan	12 months from baseline
Change in femoral neck areal bone mineral density (aBMD)	measured in g/cm2 during dual energy x-ray absorptiometry (DXA) scan	12 months from baseline
Change in distal radius areal bone mineral density (aBMD)	measured in g/cm2 during dual energy x-ray absorptiometry (DXA) scan	12 months from baseline
Change in lumbar spine areal bone mineral density (aBMD)	measured in g/cm2 during dual energy x-ray absorptiometry (DXA) scan	12 months from baseline
Change in total body fat mass (kg)	measurement taken during dual energy x-ray absorptiometry (DXA) scan	12 months from baseline
Change in total body lean mass (kg)	measurement taken during dual energy x-ray absorptiometry (DXA)	12 months from baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortical thickness (mm)	measurement taken during computed tomography (CT) scan	12 months from baseline
D3-Creatine derived muscle mass measured in kg	measurement taken via urine sample	12 months from baseline
Gait speed	measured in m/s during the 400 meter walk test	12 months from baseline
expanded Short Physical Performance Battery (eSPPB)	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 months from baseline
Timed-Up-and-Go (TUG)	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.	12 months from baseline
Stair climbing time	measured in seconds using the participant's fastest time achieved to climb a 12 step staircase in two trials.	12 months from baseline
Lower extremity muscle strength	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)	12 months from baseline
Grip strength	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	12 months from baseline
Cognitive Assessment	measured using the Montreal Cognitive Assessment (MOCA) with scores ranging from 0-30, with a score of 26 and higher generally considered normal.	12 months from baseline
Fatigability	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.	12 months from baseline
Pain and Fatigue	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.	12 months from baseline
Overall limb loading	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.	6 months from baseline
Overall satisfaction participating in the optional insole visits	overall satisfaction measured by a scale from 1-5 with a higher score indicating greater satisfaction	6 months from baseline
Mid-thigh muscle density measured in Hounsfield units (HU)	measurement taken during computed tomography (CT) scan	12 months from baseline
Mid- thigh intermuscular fat cross sectional area (CSA) (cm2)	measurement taken during computed tomography (CT) scan	12 months from baseline
Finite element (FE) modeling of bone strength measured in Kilonewton (kN)	measurement taken during computed tomography (CT) scan	12 months from baseline
Mid-thigh muscle CSA (cm2)	measurement taken during computed tomography (CT) scan	12 months from baseline
L3 muscle density measured in HU	measurement taken during computed tomography (CT) scan	12 months from baseline
L3 intermuscular fat CSA (cm2)	measurement taken during computed tomography (CT) scan	12 months from baseline
L3 muscle CSA (cm2)	measurement taken during computed tomography (CT) scan	12 months from baseline
Physical activity among older adults	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 an activities of moderate intensity (METS) score of 3.0 or higher, are considered moderate intensity.	12 months from baseline
Concentration of Procollagen 1 Intact N-Terminal Propeptide (P1NP) (ug/L)	Biomarkers of bone turnover measured via blood specimen	12 months from baseline
Concentration of C-terminal telopeptide (CTX) (pg/mL)	Biomarkers of bone turnover measured via blood specimen	12 months from baseline

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2020
• Primary Completion (Actual): April 1, 2024
• Study Completion (Actual): April 1, 2024

Study Registration Dates

• First Submitted: August 29, 2019
• First Submitted That Met QC Criteria: August 30, 2019
• First Posted (Actual): September 3, 2019

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: nutrition; vest
• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Loss
• Other Study ID Numbers: IRB00058279

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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