Clinical trial NCT04471792: Creatine Use and Muscle Stretching in Peripheral Artery Disease
Official title: Creatine Monohydrate Use and Muscle Stretching in Peripheral Artery Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Peripheral Arterial Disease
Keywords: Muscle stretch
Creatine Monohydrate
Lead sponsor: Florida State University
Sponsor class: OTHER
First posted: 2020-07-15
Enrollment: 13
Sex: ALL
Minimum age (years): 40
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Walking tolerance
timeFrame: 4 weeks
Secondary outcomes:
measure: Near infrared spectroscopy (NIRS)
timeFrame: 4 weeks
measure: Magnetic Resonance Imaging (MRI)
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Tallahassee
country: United States
facility: Florida State University
state: Florida
Study officials:
affiliation: Professor
name: Judy Muller-Delp, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hultman E, Soderlund K, Timmons JA, Cederblad G, Greenhaff PL. Muscle creatine loading in men. J Appl Physiol (1985). 1996 Jul;81(1):232-7. doi: 10.1152/jappl.1996.81.1.232.
citation: Hotta K, Behnke BJ, Arjmandi B, Ghosh P, Chen B, Brooks R, Maraj JJ, Elam ML, Maher P, Kurien D, Churchill A, Sepulveda JL, Kabolowsky MB, Christou DD, Muller-Delp JM. Daily muscle stretching enhances blood flow, endothelial function, capillarity, vascular volume and connectivity in aged skeletal muscle. J Physiol. 2018 May 15;596(10):1903-1917. doi: 10.1113/JP275459. Epub 2018 Apr 5.