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

Overseen By Mark S Nash, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Miami

Disqualifiers: Pregnancy, Breastfeeding

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This study will evaluate if Ursolic Acid supplementation may be effective in reducing muscle loss and improving blood sugar control in the SCI community.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the drug ursolic acid combined with strength training for muscle atrophy and insulin resistance in spinal cord injury?

Research shows that ursolic acid can enhance muscle growth and reduce muscle loss by improving signaling pathways involved in muscle metabolism. It has been found to improve muscle mass and function in spinal cord injury models, suggesting it may help counteract muscle atrophy and improve insulin resistance. ^{1 2 3 4 5}

Is the combination of ursolic acid and strength training safe for humans?

Research suggests that ursolic acid, a natural compound found in plants, is generally safe when used alongside strength training in humans. Studies have shown it can help with muscle development and may reduce body fat without significant adverse effects. ^{5 6 7 8 9}

How does the treatment of strength training combined with ursolic acid differ from other treatments for muscle atrophy and insulin resistance in spinal cord injury?

This treatment is unique because it combines strength training with ursolic acid, a natural compound found in apples, which enhances muscle growth and reduces atrophy by boosting mTOR signaling, a key pathway for muscle development. Unlike other treatments, this combination also improves metabolic outcomes like insulin resistance, making it a novel approach for addressing both muscle and metabolic issues in spinal cord injury. ^{1 5 6 7 8}

Research Team

Mark S Nash, PhD

Principal Investigator

University of Miami

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Strength Training (Other)
• Ursolic Acid (Other)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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, 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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effects of ursolic acid on sub-lesional muscle pathology in a contusion model of spinal cord injury. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Pharmacologic approaches to prevent skeletal muscle atrophy after spinal cord injury. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Bone and muscle loss after spinal cord injury: organ interactions. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Body-weight-support treadmill training improves blood glucose regulation in persons with incomplete spinal cord injury. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass. [2023]

6. England 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. [2023]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Concurrent treatment with ursolic acid and low-intensity treadmill exercise improves muscle atrophy and related outcomes in rats. [2020]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Ursolic Acid-induced elevation of serum irisin augments muscle strength during resistance training in men. [2020]

9. United States 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. [2023]