Targeting Hyaluronan Accumulation Through Exercise in T2DM

NCT04383314 | Completed DMC

• 1 other identifier: 19-01913
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

A pilot longitudinal study to examine hyaluronan (HA) accumulation in muscles of individuals with Type 2 diabetes mellitus (T2DM), and the effects of exercise on HA accumulation, muscle stiffness, strength, ankle joint mobility, and physical function. HA accumulation will be assessed non- invasively using magnetic resonance imaging.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (7)

• Change in the Level of Hyaluronan accumulation in calf muscle of participants

  Hyaluronan accumulation (HA) in calf muscle will be assessed using 3D T1ρ and T2-weighted MR scans on a 3T whole-body clinical MRI scanner (Prisma, Siemens Healthcare, Erlangen, Germany) with a 15-channel knee coil (QED, Cleveland OH). The total scan time is expected to be 29 min, 30 s. The sequence acquisition parameters will be as follows: TR/TE = 1500 ms/3.78 ms, flip angle = 8°, field of view (FOV) = 140 mm2, spin-lock lengths (TSLs)=0,10ms, 20ms, 30ms, 40ms and 60ms, spin-lock frequency=500Hz matrix size 256 × 128 × 64, slice thickness = 2 m.

  Week 1, Week 11

• Change in the Level of Calf muscle stiffness in participants

  Calf muscle stiffness will measured using a previously validated device (FDA product classification: non-powered goniometer, 510K exempt). Briefly, subjects are positioned supine with the knee extended and their leg is secured by Velcro straps. Torques of 15, 20 and 25 Nm are applied using a hand-held force gauge (FDK 40, Wagner Instruments, Greenwich, CT) and resultant angular kinematics are measured using a digital inclinometer (Checkpoint Inc., Torrance, CA). Three cycles of testing are performed in ascending order of force application and resultant peak dorsiflexion range of motion is recorded at each force level. Calf muscle stiffness is calculated as the slope of the resultant curves over the 15 to 25 Nm intervals. This device has demonstrated high convergent validity compared to motion analysis (Intraclass correlation coefficient (ICC \[2,k\])\> 0.95).

  Week 1, Week 11

• Change in the Degree of Passive ankle mobility in participants

  Passive ankle mobility will measured using a previously validated device (FDA product classification: non-powered goniometer, 510K exempt). Briefly, subjects are positioned supine with the knee extended and their leg is secured by Velcro straps. The axis of rotation of the device is then adjusted in the anteroposterior and supero-inferior directions to approximate the ankle axis of rotation determined by palpation of the distal tips of the medial and lateral malleoli. Torques of 15, 20 and 25 Nm are applied using a hand-held force gauge (FDK 40, Wagner Instruments, Greenwich, CT) and resultant angular kinematics are measured using a digital inclinometer (Checkpoint Inc., Torrance, CA). Three cycles of testing are performed in ascending order of force application and resultant peak dorsiflexion range of motion is recorded at each force level.

  Week 1, Week 11

• Change in the Level of Calf muscle strength in participants

  Calf muscle strength, quantified as peak plantarflexion torque. An isokinetic dynamometer (Biodex, Shirley, NY) will be used to quantify peak isokinetic torque of the calf muscle at 60 degrees per second in participants' available range of motion (FDA product classification: AC powered dynamometer, 510K exempt). All participants will be tested in the seated position. Three practice trials will be given, after which peak plantarflexion torque will be recorded from the highest of three trials. With these procedures, coefficient of variation of \<10% has been reported in individuals with T2DM, indicating good repeatability.

  Week 1, Week 11

• Change in the Change in Gait (Stride length) of participants after intervention

  The study will use a motion capture system to collect kinematic (marker) and kinetic (force plate and pressure plate) data as subjects walk barefoot at self-selected speed along a 10 m walkway. A minimum of five successful trials will be collected for each subject. A trial will be considered successful if the subject made clean force plate contact on the tested side without targeting. Stride length will be defined as the distance between consecutive initial contacts of the same limb and will be calculated using Visual3D software (C-motion Inc., USA).

  Week 1, Week 11

• Change in the Change in Gait (Walking Speed) of participants after intervention

  The study will use a motion capture system to collect kinematic (marker) and kinetic (force plate and pressure plate) data as subjects walk barefoot at self-selected speed along a 10 m walkway. A minimum of five successful trials will be collected for each subject. A trial will be considered successful if the subject made clean force plate contact on the tested side without targeting. Walking speed will be defined as distance travelled in unit time and will be calculated using Visual3D software (C-motion Inc., USA).

  Week 1, Week 11

• Change in Self-reported physical function of participants after intervention

  This will be evaluated using Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function and Pain Interference scales. PROMIS is a computer adaptive testing outcomes instrument, generated after exhaustive review, and the application of item response theory to calibrate the individual items. The higher the score indicate higher levels of physical functioning. All PROMIS measures are scored using the final re-centered item response theory (IRT) item parameters and transformed to the T-score metric (mean=50, SD=10).

  Week 1, Week 11

Secondary Outcomes (5)

• Change in the Glycemic Control

  Week 2, Week 12

• Change in the Number of participants with increased physical activity

  Week 1, Week 11

• Number of Participants who adhere to the Exercise program

  Week 12

• Number of participants with Neuropathy

  Week 1

• Number of participants with Osteoarthritis

  Week 1

Study Arms (1)

Exercise Program Group

EXPERIMENTAL

Participants will be prescribed an individualized 10-week exercise program with both aerobic and resistance components, based on the American College of Sports Medicine (ACSM) Guidelines.

Behavioral: 10-week exercise program on HA accumulation

Interventions

10-week exercise program on HA accumulation BEHAVIORAL

A 10-week exercise program with both aerobic and resistance components, based on the American College of Sports Medicine (2010), will be individually prescribed to 25 T2DM patients.Exercise training will be performed on Days 1 and 2 of each week under the supervision of licensed physical therapists. Participants will have the choice of using a treadmill or a recumbent stepper. The physical therapists will monitor blood glucose level, blood pressure, heart rate, and RPE during each exercise session. Participants will be asked to exercise at home on Day 3 of each week, and will not be supervised by the study team.

Exercise Program Group

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be between the ages of 40 and 75
• Clinical diagnosis of Type 2 diabetes
• Have a BMI less than 40 kg/m2 (due to magnet bore restrictions)
• Able to walk unassisted

You may not qualify if:

• Serious cardiac pathology or musculoskeletal problems that would limit exercise ability
• Current open wound or history of plantar ulcer for the last 3 months
• Partial foot amputations
• Inability to ambulate without assistive device
• Stroke or other central nervous system pathology
• Stage 2 hypertension (resting blood pressure \>160 systolic or \>100 diastolic)
• Contraindications to 3T whole body MRI scanners (e.g., pacemaker, cerebral aneurysm clip, cochlear implant, presence of shrapnel in strategic locations, metal in the eye, claustrophobia, or other problems).
• Subjects with alcoholism, chronic drug use, chronic gastrointestinal disease, or renal or hepatic impairment
• Pregnant women and children

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Smita Rao, PhD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2020
• First Posted: May 12, 2020
• Study Start: September 1, 2021
• Primary Completion: May 31, 2023
• Study Completion: August 31, 2024
• Last Updated: January 31, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Available after accepted for publication in a peer-reviewed journal.
• Access Criteria: Requests should be directed to smita.rao@nyu.edu. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)