Peripheral Arterial Disease
Conditions
Keywords
Muscle stretch, Creatine Monohydrate
Brief summary
To utilize near-infrared spectroscopy to investigate if the research device, which induces muscle stretching, and creatine loading impact submaximal exercise performance in aged and PAD patients. Near-infrared spectroscopy (NIRS)-derived tissue oxygenation responses will be obtained during device placement (muscle stretch) and during a walking test (i.e., six-minute walk test). Muscle oxygenation at rest and during device placement will be assessed with Magnetic Resonance Imaging. It is hypothesized that the stretching protocol will improve both NIRS-derived tissue oxygenation and magnetic resonance-derived muscle oxygenation and that creatine supplementation will further improve phosphorus metabolite muscle performance. All patients will undergo either 4 weeks of stretch training with- or- without creatine supplementation according to previously defined creatine guidelines.
Detailed description
Lower extremity peripheral artery disease (PAD) has been estimated to impact nearly 8.5 million U.S. adults above the age of 40, significantly increasing the rate of morbidity and mortality with concomitant decreases in quality of life. These patients are often given medical therapy (e.g., statins, antiplatelet, anticoagulants) and are also recommended to begin structured exercise programs. However, the limb ischemia that occurs during physical activity in these patients often limits exercise tolerance. A previous study by Bauer and colleagues showed that impaired muscle metabolism is a major contributor to functional limitations in PAD patients. These data are important in that they show alterations in blood flow and metabolic machinery likely impact exercise tolerance. As such, the development of tolerable countermeasures to improve limb blood flow and muscle energetics may increase adherence to exercise therapy and improve health outcomes in PAD patients. Previous work by the investigators has shown that daily muscle stretching, achieved via 30-minutes of ankle dorsiflexion, significantly improved soleus muscle function and muscle blood flow during exercise in a rat model of aging . In a follow-up study, the investigators have also shown that this model improves vascular function and walking function in PAD patients. As noted above, muscle energetics are delayed in PAD patients, so improving the rest-to-exercise transition with creatine supplementation may help PAD patients sustain exercise longer. The investigators are now testing to see if an added supplement can further improve the effects of muscle stretching in PAD patients.
Interventions
DRUGCreatine monohydrate
Creatine monohydrate will be used in combination with muscle stretching.
DIETARY_SUPPLEMENTCellulose
Cellulose will be used in combination with muscle stretching.
Sponsors
Florida State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Randomized, single-blind research design.
Eligibility
Sex/Gender
ALL
Age
40 Years to 95 Years
Healthy volunteers
Yes
Inclusion criteria
1. Ankle-brachial index (ABI) of 0.90 or less in either leg or clinical diagnosis by a medical doctor (PAD group only) 2. Stable condition for at least 3 months (PAD group only)
Exclusion criteria
1. Habitual exercise or cardiovascular rehabilitation program during the past 3 months 2. Critical limb ischemia 3. Blow or above-knee amputation 4. Leg pain at rest 5. Major surgery or lower extremity revascularization in the last 3 months 6. Major medical illness treatment during the prior 12 months 7. Central neurological disease 8. Limited ankle or knee joint range of motion 9. Requirement of oxygen with activity or exercise 10. Heart failure 11. Atrial fibrillation 12. Wheelchair confinement or inability to walk 13. Cognitive disorder 14. Vasculitis problems including Takayasu's arteritis, Berger's disease, collagen disease or Reynaud's disease 15. Overt cardiovascular disease 16. Metabolic disease 17. Renal disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Walking Distance | Baseline and after 4 weeks of intervention | 6-minute walking test. This test measures the distance (in meters) that a patient can walk in 6 minutes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Percent Oxygenation/Seconds | Baseline and after 4 weeks of intervention | Near-infrared spectroscopy (NIRS) will be used to measure changes in oxygen saturation (%) in the gastrocnemius muscle. Measurement will be the rate (slope) of the change in oxygen saturation (StO2) per second. Thus rate of rate in oxygenation (slope) = StO2(%)/s = Δ StO2(%)/s |
Countries
United States
Participant flow
Recruitment details
33 patients were screened. 3 patients were ineligible due to kidney disease and resting leg pain. Thirty patients met eligibility criteria. 8 patients did not respond to follow up and 9 patients lost interest. 13 patients consented to participate and were randomly assigned to either stretch+creatine or stretch+placebo. Zero healthy control participants were enrolled. Only participants with Peripheral Artery Disease were enrolled and randomized to either stretch+creatine or stretch+placebo.
Pre-assignment details
All 13 patients that were consented completed baseline testing and randomization to either stretch +creatine or stretch + placebo.
Participants by arm
| Arm | Count |
|---|---|
| Creatine Monohydrate Creatine Monohydrate will be given at a 5 day loading period (10g/day) followed by a maintenance phase (5 g/day). The objectives of the current trial are to investigate if creatine supplementation plus muscle stretching improves 6-minute walking distance and muscle oxygenation in patients with peripheral artery disease.
Creatine monohydrate: Creatine monohydrate will be used in combination with muscle stretching. | 7 |
| Cellulose These participants will consume a fiber supplement in place of creatine monohydrate at a matched dose with muscle stretching.
Cellulose: Cellulose will be used in combination with muscle stretching. | 6 |
| Total | 13 |
Baseline characteristics
| Characteristic | Cellulose | Total | Creatine Monohydrate |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 11 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 1 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 6 Participants | 13 Participants | 7 Participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 7 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 |
| other Total, other adverse events | 0 / 7 | 0 / 6 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 |
Outcome results
Primary
Walking Distance
6-minute walking test. This test measures the distance (in meters) that a patient can walk in 6 minutes.
Time frame: Baseline and after 4 weeks of intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Creatine Monohydrate | Walking Distance | Baseline 6MWT Distance | 375 meters | Standard Deviation 84 |
| Creatine Monohydrate | Walking Distance | Post-stretching 6MWT Distance | 405 meters | Standard Deviation 65 |
| Cellulose | Walking Distance | Baseline 6MWT Distance | 411 meters | Standard Deviation 72 |
| Cellulose | Walking Distance | Post-stretching 6MWT Distance | 425 meters | Standard Deviation 83 |
p-value: 0.38ANOVA
Secondary
Change in Percent Oxygenation/Seconds
Near-infrared spectroscopy (NIRS) will be used to measure changes in oxygen saturation (%) in the gastrocnemius muscle. Measurement will be the rate (slope) of the change in oxygen saturation (StO2) per second. Thus rate of rate in oxygenation (slope) = StO2(%)/s = Δ StO2(%)/s
Time frame: Baseline and after 4 weeks of intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Creatine Monohydrate | Change in Percent Oxygenation/Seconds | Baseline Δ StO2(%)/s | 0.59 delta StO2 (%/delta time(s) | Standard Deviation 0.12 |
| Creatine Monohydrate | Change in Percent Oxygenation/Seconds | Post-stretching Δ StO2(%)/s | 0.64 delta StO2 (%/delta time(s) | Standard Deviation 0.52 |
| Cellulose | Change in Percent Oxygenation/Seconds | Baseline Δ StO2(%)/s | 0.59 delta StO2 (%/delta time(s) | Standard Deviation 0.4 |
| Cellulose | Change in Percent Oxygenation/Seconds | Post-stretching Δ StO2(%)/s | 0.67 delta StO2 (%/delta time(s) | Standard Deviation 0.44 |
p-value: 0.883ANOVA
p-value: 0.883ANOVA