Creatine Use and Muscle Stretching in Peripheral Artery Disease

• Sponsor: Florida State University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04471792
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 31.6
• Patients Per Site Per Month: 1.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Peripheral Arterial Disease	Drug: Creatine monohydrate; Dietary Supplement: Cellulose	Phase 2

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Masking Description: Randomized, single-blind research design.
• Primary Purpose: Treatment
• Official Title: Creatine Monohydrate Use and Muscle Stretching in Peripheral Artery Disease
• Actual Study Start Date: May 12, 2020
• Anticipated Primary Completion Date: Dec 31, 2022
• Anticipated Study Completion Date: Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Creatine monohydrate; Creatine monohydrate will be used in combination with muscle stretching.
Placebo Comparator: Cellulose These participants will consume a fiber supplement in place of creatine monohydrate at a matched dose with muscle stretching.	Dietary Supplement: Cellulose; Cellulose will be used in combination with muscle stretching.

Outcome Measures

Primary Outcome Measures

1. Walking tolerance [4 weeks]

   All patients will perform a pre -and -post 6 minute walking test to assess functional outcomes of muscle stretching and supplementation

Secondary Outcome Measures

1. Near infrared spectroscopy (NIRS) [4 weeks]

   Use of NIRS on the lateral head of the gastrocnemius muscle in all patients will be performed. NIRS will be measured during a vascular occlusion test, during placement of splint device, and the 6 minute walking test.

2. Magnetic Resonance Imaging (MRI) [4 weeks]

   Use of MRI to assess muscle oxygenation during a vascular occlusion test at rest, and during placement of splint device

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 95 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Florida State University	Tallahassee	Florida	United States	32304

Sponsors and Collaborators

• Florida State University

Investigators

• Principal Investigator: Judy Muller-Delp, Ph.D., Professor

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• Hultman E, Söderlund K, Timmons JA, Cederblad G, Greenhaff PL. Muscle creatine loading in men. J Appl Physiol (1985). 1996 Jul;81(1):232-7.

• Responsible Party: Judy Delp, Professor, Florida State University
• ClinicalTrials.gov Identifier: NCT04471792
• Other Study ID Numbers: 1150
• First Posted: Jul 15, 2020
• Last Update Posted: Mar 18, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Judy Delp, Professor, Florida State University: Muscle stretch; Creatine Monohydrate
• Additional relevant MeSH terms: Peripheral Arterial Disease; Peripheral Vascular Diseases

Study Results

No Results Posted as of Mar 18, 2022