Ursolic Acid + Strength Training for Muscle Atrophy and Insulin Resistance in Spinal Cord Injury

Overseen By Mark S Nash, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Miami

Disqualifiers: Pregnancy, Breastfeeding

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether Ursolic Acid, a natural compound, can reduce muscle loss and improve blood sugar control in individuals with spinal cord injuries. Participants will either take Ursolic Acid supplements and engage in strength training or only take the supplements. The trial targets those who have had a spinal cord injury for over a year, affecting either the upper back (T2-T8) or neck area (C4-C7). The study aims to find better ways to manage muscle weakness and insulin resistance after a spinal cord injury. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ursolic acid is generally safe as a dietary supplement. Studies have found that people usually tolerate it well, without serious side effects. Specifically, research on spinal cord injury demonstrated that ursolic acid can safely improve muscle health.

Regarding strength training, previous studies have found it safe and well-tolerated for people with spinal cord injuries. Resistance exercises, even at a moderate level, have boosted muscle strength and overall health without major side effects.

The combination of ursolic acid and strength training appears safe based on current research. However, discussing potential risks with a healthcare provider before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for muscle atrophy and insulin resistance in spinal cord injury, which often include medications and physical therapy, this new approach combines strength training with ursolic acid (UA), a natural compound found in apple peels. Researchers are excited about UA because it may help build muscle and improve insulin sensitivity, offering a novel mechanism of action compared to existing treatments. The combination of UA with exercise could provide a more effective and holistic strategy to combat these issues, potentially improving the quality of life for those with spinal cord injuries.

What evidence suggests that this trial's treatments could be effective for muscle atrophy and insulin resistance in spinal cord injury?

This trial will compare the effects of Ursolic Acid and strength training on muscle atrophy and insulin resistance in individuals with spinal cord injuries. Research has shown that Ursolic Acid, a natural substance, can help prevent muscle loss by supporting muscle growth. Early findings also suggest it might help control blood sugar levels. Strength training has greatly increased muscle strength in people with spinal cord injuries. Studies indicate that even short-term resistance training, lasting 6–12 weeks, can effectively build muscle strength. Together, these treatments offer hope for addressing muscle loss and blood sugar issues in spinal cord injury cases. Participants in this trial will receive either Ursolic Acid alone or in combination with strength training, depending on their assigned treatment arm. ^{1 6 7 8 9}

Who Is on the Research Team?

Mark S Nash, PhD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for men and women with chronic spinal cord injuries, either paraplegia or quadriplegia, that have lasted more than a year. It's open to those with varying degrees of injury severity from specific regions of the spine (T2-T8 for paraplegia and C4-C7 for quadriplegia). Pregnant or breastfeeding individuals cannot participate.

Inclusion Criteria

I have had a spinal cord injury between C4-C7 for over a year.

I have had a spinal cord injury between T2-T8 for over a year, affecting my ability to move.

Exclusion Criteria

Pregnant or planning to become pregnant

Women who are breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take Ursolic Acid (UA) 4 capsules twice daily for 12 weeks. Participants in the paraplegia group also participate in an exercise program 3 times per week.

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Strength Training
• Ursolic Acid

Trial Overview

The study is testing whether Ursolic Acid supplements can help reduce muscle loss and improve blood sugar control in people with chronic spinal cord injuries. Participants will also engage in strength training as part of the intervention.

How Is the Trial Designed?

Group I: UA in tetraplegia group Experimental Treatment 1 Intervention

Participants will take UA 4 capsules twice daily for 12 weeks

Group II: UA and exercise in paraplegia group Experimental Treatment 2 Interventions

Participants will take UA 4 capsules twice daily for 12 weeks while participating in an exercise program, 3 times per week.

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Florida

Collaborator

Trials

10

Recruited

1,100+

Published Research Related to This Trial

In a study involving male Sprague-Dawley rats with induced muscle atrophy, the combination of ursolic acid (UA) and low-intensity treadmill exercise significantly improved muscle mass and reduced body weight and visceral fat compared to UA alone.

The concurrent treatment (UA plus exercise) effectively decreased the expression of muscle atrophy-related genes, indicating a potential mechanism for combating muscle atrophy-related diseases, while also enhancing endurance capacity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent treatment with ursolic acid and low-intensity treadmill exercise improves muscle atrophy and related outcomes in rats. Kim, JC., Kang, YS., Noh, EB., et al.[2020]

In an 8-week double-blind, placebo-controlled trial involving 22 young men, both ursolic acid (UA) and placebo groups showed significant increases in body weight, body mass index, and thigh circumference, indicating that resistance training combined with a high-protein diet effectively promotes muscle growth.

However, there was no significant difference in muscle strength or mass between the UA and placebo groups, suggesting that ursolic acid does not enhance the effects of resistance training in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ursolic acid has no additional effect on muscle strength and mass in active men undergoing a high-protein diet and resistance training: A double-blind and placebo-controlled trial. Lobo, PCB., Vieira, IP., Pichard, C., et al.[2023]

Spinal cord injury (SCI) leads to significant muscle and bone loss, with modest muscle activity helping to prevent atrophy, but much greater bone loading is needed to prevent irreversible bone loss.

SCI is associated with hormonal deficiencies (like growth hormone and testosterone) that may worsen muscle and bone loss, contributing to higher rates of insulin resistance and diabetes in affected individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone and muscle loss after spinal cord injury: organ interactions. Qin, W., Bauman, WA., Cardozo, C.[2022]

In a study of 16 healthy men undergoing 8 weeks of resistance training, those who took ursolic acid (UA) showed a significant decrease in body fat percentage and increases in muscle strength compared to those who did not take UA.

The results suggest that UA may enhance skeletal muscle development by increasing levels of insulin-like growth factor-1 (IGF-1) and irisin, which are important for muscle growth and strength.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ursolic Acid-induced elevation of serum irisin augments muscle strength during resistance training in men. Bang, HS., Seo, DY., Chung, YM., et al.[2020]

Skeletal muscle atrophy following severe spinal cord injury (SCI) is driven by a combination of factors including systemic inflammation and hormonal changes, leading to rapid muscle loss due to disrupted IGF-1/PI3K/Akt signaling.

While traditional anabolic agents like androgens are less effective in preventing SCI-induced muscle atrophy, compounds like ursolic acid and β2-agonists show promise in reducing muscle loss, especially when combined with physical rehabilitation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic approaches to prevent skeletal muscle atrophy after spinal cord injury. Otzel, DM., Kok, HJ., Graham, ZA., et al.[2022]

Ursolic acid, a natural compound found in apples, has been identified as a potential therapy for skeletal muscle atrophy, showing the ability to reduce muscle loss and promote muscle growth in mice.

The mechanism of action involves enhancing insulin/IGF-I signaling in skeletal muscle and reducing the expression of mRNAs associated with muscle atrophy, while also improving metabolic health by lowering fat, blood glucose, and cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass. Kunkel, SD., Suneja, M., Ebert, SM., et al.[2023]

In a study involving nine resistance-trained men, ingestion of 3 grams of l-leucine after exercise significantly increased skeletal muscle IGF-1 levels compared to a placebo, indicating its effectiveness in promoting muscle growth.

Ursolic acid did not show any significant effects on Akt/mTORC1 signaling or serum insulin and IGF-1 levels, suggesting that while it increases in plasma after exercise, it may not enhance muscle growth in the same way as l-leucine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

l-Leucine Increases Skeletal Muscle IGF-1 but Does Not Differentially Increase Akt/mTORC1 Signaling and Serum IGF-1 Compared to Ursolic Acid in Response to Resistance Exercise in Resistance-Trained Men. Church, DD., Schwarz, NA., Spillane, MB., et al.[2023]

A 6-month body-weight-supported treadmill training program significantly improved glucose regulation in nine individuals with incomplete spinal cord injury, evidenced by a 15% reduction in glucose area under the curve and a 33% reduction in insulin area under the curve after training.

The training enhanced muscle metabolic characteristics, including a 80% increase in muscle glycogen and improved glucose transport and phosphorylation capabilities, which likely contributed to better glucose homeostasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Body-weight-support treadmill training improves blood glucose regulation in persons with incomplete spinal cord injury. Phillips, SM., Stewart, BG., Mahoney, DJ., et al.[2013]

Ursolic acid (UA) treatment significantly enhances mTOR signaling in mice with spinal cord injury (SCI), which helps counteract muscle atrophy and improve muscle mass and function.

In addition to improving muscle mass, UA treatment also leads to better motor coordination and strength, suggesting it could be a promising therapeutic strategy for addressing muscle-related issues following SCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ursolic acid on sub-lesional muscle pathology in a contusion model of spinal cord injury. Bigford, GE., Darr, AJ., Bracchi-Ricard, VC., et al.[2023]

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