Diabetes, Peripheral Neuropathy
Conditions
Keywords
Exercise
Brief summary
This project proposes a longitudinal design that uses multinuclear-MRI to evaluate the mechanistic effects of exercise on skeletal muscle function and peripheral nerve integrity in patients with diabetic peripheral neuropathy (DPN), and to determine whether exercise can reverse DPN symptoms. The investigators will prescribe a 10-week exercise program to 40 DPN patients. The investigators will acquire multinuclear-MRI data before and after the intervention that can provide mechanistic insight into the adaptations in lower leg muscle function and peripheral nerve integrity of patients with DPN, and their role in improving DPN symptoms following physical exercise intervention.
Interventions
PROCEDUREExercise Program
The exercise program will combine moderate intensity aerobic exercise with lower-extremity specific resistance training. A moderate level of intensity will be calculated based on results from a maximal graded exercise test (VO2R) conducted prior to the intervention.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NYU Langone Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Be between the ages of 40 and 70 * Clinical diagnosis of Type 2 diabetes * Clinical diagnosis of DPN * Have a BMI less than 40 kg/m2 (due to magnet bore restrictions) * Able to walk unassisted
Exclusion criteria
* Serious cardiac pathology or musculoskeletal problems that would limit exercise ability * MNSI score \< 1 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Body Mass Index (BMI) | Baseline | The BMI calculation divides an adult's weight in kilograms by their height in meters squared. |
| Change From Baseline in Body Mass Index (BMI) | Week 10 | The BMI calculation divides an adult's weight in kilograms by their height in meters squared. |
| Glycosylated Hemoglobin (HbA1c) | Baseline | The glycosylated hemoglobin test shows what a person's average blood glucose level was for the 2 to 3 months before the test. Measured via patient blood samples. |
| C-Reactive Protein Levels | Baseline | Measured via patient blood samples. |
| Michigan Neuropathy Screening Instrument (MNSI) Symptom Questionnaire | Baseline | 15-question assessment of symptoms. Responses of yes to items 1-3, 5-6, 8-9, 11-12, 14-15 are each counted as one point. A no response on items 7 and 13 counts as 1 point. Item 4 is a measure of impaired circulation and item 10 is a measure of general asthenia; neither are included in scoring. The total score ranges from 0-13; lower scores indicate less prevalent symptoms; a decrease in scores indicates symptoms decreased during the observational period. |
| MNSI Physical Exam Score | Baseline | Completed by physician. Assessment of abnormalities in the appearance of the feet, vibration sense, reflexes, and monofilament sensation. The total score ranges from 0-10; lower scores indicate greater physical health; a decrease in scores indicates physical health increased during the observational period. |
| Calf Muscle Performance | Baseline | Performance will be quantified as peak ankle plantarflexion torque at 60 degrees/sec. |
| Physical Performance Test (PP) Score | Baseline | 9-item assessment of Physical Performance. The total score ranges from 0 to 36; higher scores indicate greater levels of physical performance. |
| PCr Resynthesis Rate in the Gastrocnemius Muscle Groups | Baseline | Measured using multinuclear-MRI following a 90-second plantar flexion exercise during which resistance is applied at approximately 40% of the individual's maximum voluntary contraction. The value reported in the data table represents the average flexion across both calf muscles. |
| Intramuscular Adipose Tissue (IMAT) Levels in the Gastrocnemius Muscle Groups | Baseline | Measured using IDEAL-MRI. IMAT levels are quantified as a percentage of total tissue in the gastrocnemius muscle groups of both calf muscles combined. |
| IMAT Levels in the Soleus Muscle Groups | Baseline | Measured using IDEAL-MRI. IMAT levels are quantified as a percentage of total tissue in the soleus muscle groups of both calf muscles combined. |
| Fractional Anisotropy (FA) in the Tibial Nerve | Baseline | FA is a scalar value between zero and one that describes the degree of anisotropy of a diffusion process. A value of zero means that diffusion is isotropic, i.e. it is unrestricted (or equally restricted) in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions. Measured using Diffusion Tensor Imaging (DTI). |
| Apparent Diffusion Coefficient (ADC) in the Tibial Nerve | Baseline | ADC is a measure of the magnitude of diffusion (of water molecules) within tissue. Measured using DTI. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN Patients will be individually prescribed to a 10-week exercise program with both aerobic and resistance components. Prior to beginning the intervention, patients will participate in a maximal graded exercise test (VO2R) using a cycle ergometer with a metabolic cart and integrated ECG.
Exercise Program: The exercise program will combine moderate intensity aerobic exercise with lower-extremity specific resistance training. A moderate level of intensity will be calculated based on results from a maximal graded exercise test (VO2R) conducted prior to the intervention. | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | lost to follow up (study interrupted by COVID) | 6 |
| Overall Study | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | Patients With Type 2 Diabetes and Clinical Symptoms of DPN |
|---|---|
| Age, Continuous | 61.4 years STANDARD_DEVIATION 8.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 44 |
| other Total, other adverse events | 5 / 44 |
| serious Total, serious adverse events | 0 / 44 |
Outcome results
Primary
Apparent Diffusion Coefficient (ADC) in the Tibial Nerve
ADC is a measure of the magnitude of diffusion (of water molecules) within tissue. Measured using DTI.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | Apparent Diffusion Coefficient (ADC) in the Tibial Nerve | 1.76 x10^3 mm^2/s | Standard Deviation 0.2 |
Primary
Apparent Diffusion Coefficient (ADC) in the Tibial Nerve
ADC is a measure of the magnitude of diffusion (of water molecules) within tissue. Measured using DTI.
Time frame: Week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | Apparent Diffusion Coefficient (ADC) in the Tibial Nerve | 1.81 x10^3 mm^2/s | Standard Deviation 0.19 |
Primary
Body Mass Index (BMI)
The BMI calculation divides an adult's weight in kilograms by their height in meters squared.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | Body Mass Index (BMI) | 30.7 kg/m^2 | Standard Deviation 4.2 |
Primary
Calf Muscle Performance
Performance will be quantified as peak ankle plantarflexion torque at 60 degrees/sec.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | Calf Muscle Performance | 35 newton-meters | Standard Deviation 15 |
Primary
Calf Muscle Performance
Performance will be quantified as peak ankle plantarflexion torque at 60 degrees/sec.
Time frame: Week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | Calf Muscle Performance | 44 newton-meters | Standard Deviation 19 |
Primary
Change From Baseline in Body Mass Index (BMI)
The BMI calculation divides an adult's weight in kilograms by their height in meters squared.
Time frame: Week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | Change From Baseline in Body Mass Index (BMI) | 30.2 kg/m^2 | Standard Deviation 4.1 |
Primary
C-Reactive Protein Levels
Measured via patient blood samples.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | C-Reactive Protein Levels | 4.5 mg/L | Standard Deviation 3.8 |
Primary
C-Reactive Protein Levels
Measured via patient blood samples.
Time frame: Week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | C-Reactive Protein Levels | 4.6 mg/L | Standard Deviation 4.5 |
Primary
Fractional Anisotropy (FA) in the Tibial Nerve
FA is a scalar value between zero and one that describes the degree of anisotropy of a diffusion process. A value of zero means that diffusion is isotropic, i.e. it is unrestricted (or equally restricted) in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions. Measured using Diffusion Tensor Imaging (DTI).
Time frame: Week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | Fractional Anisotropy (FA) in the Tibial Nerve | 0.33 score on a scale | Standard Deviation 0.05 |
Primary
Fractional Anisotropy (FA) in the Tibial Nerve
FA is a scalar value between zero and one that describes the degree of anisotropy of a diffusion process. A value of zero means that diffusion is isotropic, i.e. it is unrestricted (or equally restricted) in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions. Measured using Diffusion Tensor Imaging (DTI).
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | Fractional Anisotropy (FA) in the Tibial Nerve | 0.32 score on a scale | Standard Deviation 0.07 |
Primary
Glycosylated Hemoglobin (HbA1c)
The glycosylated hemoglobin test shows what a person's average blood glucose level was for the 2 to 3 months before the test. Measured via patient blood samples.
Time frame: Week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | Glycosylated Hemoglobin (HbA1c) | 7.3 percentage (%) of HbA1c | Standard Deviation 1.2 |
Primary
Glycosylated Hemoglobin (HbA1c)
The glycosylated hemoglobin test shows what a person's average blood glucose level was for the 2 to 3 months before the test. Measured via patient blood samples.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | Glycosylated Hemoglobin (HbA1c) | 7.4 percentage (%) of HbA1c | Standard Deviation 1.2 |
Primary
IMAT Levels in the Soleus Muscle Groups
Measured using IDEAL-MRI. IMAT levels are quantified as a percentage of total tissue in the soleus muscle groups of both calf muscles combined.
Time frame: Week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | IMAT Levels in the Soleus Muscle Groups | 9.9 percentage of tissue | Standard Deviation 4.2 |
Primary
IMAT Levels in the Soleus Muscle Groups
Measured using IDEAL-MRI. IMAT levels are quantified as a percentage of total tissue in the soleus muscle groups of both calf muscles combined.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | IMAT Levels in the Soleus Muscle Groups | 9.8 percentage of tissue | Standard Deviation 4.1 |
Primary
Intramuscular Adipose Tissue (IMAT) Levels in the Gastrocnemius Muscle Groups
Measured using IDEAL-MRI. IMAT levels are quantified as a percentage of total tissue in the gastrocnemius muscle groups of both calf muscles combined.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | Intramuscular Adipose Tissue (IMAT) Levels in the Gastrocnemius Muscle Groups | 9.1 percentage of tissue | Standard Deviation 4.5 |
Primary
Intramuscular Adipose Tissue (IMAT) Levels in the Gastrocnemius Muscle Groups
Measured using IDEAL-MRI. IMAT levels are quantified as a percentage of total tissue in the gastrocnemius muscle groups of both calf muscles combined.
Time frame: Week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | Intramuscular Adipose Tissue (IMAT) Levels in the Gastrocnemius Muscle Groups | 9 percentage of tissue | Standard Deviation 4.5 |
Primary
Michigan Neuropathy Screening Instrument (MNSI) Symptom Questionnaire
15-question assessment of symptoms. Responses of yes to items 1-3, 5-6, 8-9, 11-12, 14-15 are each counted as one point. A no response on items 7 and 13 counts as 1 point. Item 4 is a measure of impaired circulation and item 10 is a measure of general asthenia; neither are included in scoring. The total score ranges from 0-13; lower scores indicate less prevalent symptoms; a decrease in scores indicates symptoms decreased during the observational period.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | Michigan Neuropathy Screening Instrument (MNSI) Symptom Questionnaire | 5.7 score on a scale | Standard Deviation 1.9 |
Primary
Michigan Neuropathy Screening Instrument (MNSI) Symptom Questionnaire
15-question assessment of symptoms. Responses of yes to items 1-3, 5-6, 8-9, 11-12, 14-15 are each counted as one point. A no response on items 7 and 13 counts as 1 point. Item 4 is a measure of impaired circulation and item 10 is a measure of general asthenia; neither are included in scoring. The total score ranges from 0-13; lower scores indicate less prevalent symptoms; a decrease in scores indicates symptoms decreased during the observational period.
Time frame: Week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | Michigan Neuropathy Screening Instrument (MNSI) Symptom Questionnaire | 4.8 score on a scale | Standard Deviation 2.2 |
Primary
MNSI Physical Exam Score
Completed by physician. Assessment of abnormalities in the appearance of the feet, vibration sense, reflexes, and monofilament sensation. The total score ranges from 0-10; lower scores indicate greater physical health; a decrease in scores indicates physical health increased during the observational period.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | MNSI Physical Exam Score | 3.3 score on a scale | Standard Deviation 1.3 |
Primary
MNSI Physical Exam Score
Completed by physician. Assessment of abnormalities in the appearance of the feet, vibration sense, reflexes, and monofilament sensation. The total score ranges from 0-10; lower scores indicate greater physical health; a decrease in scores indicates physical health increased during the observational period.
Time frame: Week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | MNSI Physical Exam Score | 3.2 score on a scale | Standard Deviation 1.7 |
Primary
PCr Resynthesis Rate in the Gastrocnemius Muscle Groups
Measured using multinuclear-MRI following a 90-second plantar flexion exercise during which resistance is applied at approximately 40% of the individual's maximum voluntary contraction. The value reported in the data table represents the average flexion across both calf muscles.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | PCr Resynthesis Rate in the Gastrocnemius Muscle Groups | 35.4 mM/seconds | Standard Deviation 21.8 |
Primary
PCr Resynthesis Rate in the Gastrocnemius Muscle Groups
Measured using multinuclear-MRI following a 90-second plantar flexion exercise during which resistance is applied at approximately 40% of the individual's maximum voluntary contraction. The value reported in the data table represents the average flexion across both calf muscles.
Time frame: Week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | PCr Resynthesis Rate in the Gastrocnemius Muscle Groups | 32.3 mM/seconds | Standard Deviation 21.7 |
Primary
Physical Performance Test (PP) Score
9-item assessment of Physical Performance. The total score ranges from 0 to 36; higher scores indicate greater levels of physical performance.
Time frame: Week 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | Physical Performance Test (PP) Score | 33.1 score on a scale | Standard Deviation 2.7 |
Primary
Physical Performance Test (PP) Score
9-item assessment of Physical Performance. The total score ranges from 0 to 36; higher scores indicate greater levels of physical performance.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Type 2 Diabetes and Clinical Symptoms of DPN | Physical Performance Test (PP) Score | 31.5 score on a scale | Standard Deviation 3.5 |