Neuromuscular Electrical Stimulation for Insulin Resistance

Overseen By Sudip Bajpeyi, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas, El Paso

Must not be taking: Anti-hypertensives, Lipid-lowering, Insulin sensitizers

Disqualifiers: Alcohol, Drug abuse, Smoking, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 8 weeks

80 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial excludes people who are using anti-hypertensive, lipid-lowering, or insulin sensitizing medications, so you would need to stop taking these medications to participate.

What data supports the effectiveness of the treatment Neuromuscular Electrical Stimulation for improving insulin resistance?

Research shows that Neuromuscular Electrical Stimulation (NMES) can improve glucose tolerance and insulin sensitivity, especially in people who are overweight or have type 2 diabetes. Studies have found that NMES increases energy use and helps the body manage sugar better, making it a promising option for improving metabolic health. ^{1 2 3 4 5}

Is neuromuscular electrical stimulation (NMES) safe for humans?

Neuromuscular electrical stimulation (NMES) is generally considered safe for humans, but it can cause discomfort, muscle fatigue, and in rare cases, muscle damage. It is important to monitor for any unexpected reactions, especially if there is a possibility of nerve damage. ^{1 2 6 7 8}

How does the treatment Neuromuscular Electrical Stimulation (NMES) differ from other treatments for insulin resistance?

Neuromuscular Electrical Stimulation (NMES) is unique because it uses electrical impulses to stimulate muscle contractions, which can improve muscle metabolism and insulin sensitivity without the need for physical exercise. This is different from traditional treatments like exercise, which require physical activity to achieve similar metabolic benefits. ^{9 10 11 12 13}

What is the purpose of this trial?

Once written consent is obtained, the participant will be provided with an accelerometer to be worn for 7 days to assess current physical activity levels. Subjects will be provided with a standardized diet (55/15/30% CHO/PRO/FAT) prior to collection of pre-intervention data of insulin sensitivity. Individuals will then participate in an 8-week electrical stimulation intervention (30min/day, 3x/week) and randomized into placebo/control, NMES, resistance training combined with NMES (RT +NMES), or resistance training (RT) group (n=20 per group), followed by collection of post-intervention data. The control group will receive electrical stimulation up to sensory level, the NMES group will receive stimulation up to tolerable intensity to induce visible muscle contraction, the RT+ NMES will receive stimulation up to tolerable intensity during resistance training, and the RT group will only receive exercise training. Control and NMES group will self administer stimulation at home. Pre-and post-intervention data includes measurements for body composition, resting metabolic rate, VO2max, insulin sensitivity, and comprehensive blood work.

Eligibility Criteria

This trial is for individuals with insulin resistance who are willing to follow a specific diet and participate in an 8-week study involving different types of muscle stimulation and exercise. Participants will be divided into groups, some receiving neuromuscular electrical stimulation (NMES), others doing resistance training, or both. They must wear an accelerometer for a week before the study starts.

Inclusion Criteria

My BMI is 25 or higher.

Sedentary Lifestyle: Physical Activity Level <1.4

Less than 150min/week of structured Exercise

Exclusion Criteria

I am taking medication for high blood pressure, cholesterol, or to control my blood sugar.

Excessive alcohol, drug abuse, smoking

Pregnant Women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Pre-intervention Assessment

Participants wear an accelerometer for 7 days and follow a standardized diet to assess physical activity levels and collect pre-intervention data on insulin sensitivity

1 week

1 visit (in-person)

Treatment

Participants undergo an 8-week electrical stimulation intervention, randomized into different groups (placebo/control, NMES, RT + NMES, RT), with data collection post-intervention

8 weeks

3 visits (in-person), self-administered at home

Follow-up

Participants are monitored for safety and effectiveness after treatment, including measurements for body composition, resting metabolic rate, VO2max, insulin sensitivity, and comprehensive blood work

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Neuromuscular Electrical Stimulation

Trial Overview The trial tests if neuromuscular electrical stimulation can improve metabolism in people with insulin resistance. It compares NMES alone, resistance training alone, a combination of both, and a control group getting sensory-level stimulation without muscle contractions.

Participant Groups

Group I: Resistance Training + NMES Experimental Treatment 2 Interventions

Participants will receive exercise training with stimulation up to maximum tolerable intensity.

Group II: NMES Experimental Treatment 1 Intervention

Participants will receive stimulation up to maximum tolerable level.

Group III: Resistance Training Placebo Group 2 Interventions

Participants will receive exercise training with stimulation up to sensory level.

Group IV: Control Placebo Group 1 Intervention

Participants will receive stimulation only up to sensory level.

Neuromuscular Electrical Stimulation is already approved in United States, European Union for the following indications:

Approved in United States as NMES for:

• Improving glycemic control in individuals with type 2 diabetes and obesity

Approved in European Union as Electrical Muscle Stimulation for:

• Management of type 2 diabetes
• Improvement of insulin sensitivity

Who Is Running the Clinical Trial?

University of Texas, El Paso

Lead Sponsor

Trials

17

Recruited

3,000+

Findings from Research

A 4-week study involving 10 sedentary overweight or obese adults showed that neuromuscular electrical stimulation (NMES) significantly improved glucose tolerance compared to a control group, indicating its potential as an effective intervention for metabolic health.

Despite the improvements in glucose tolerance, NMES did not result in changes in substrate utilization or muscle mass, suggesting that while NMES can enhance metabolic function, it may not directly increase muscle size or energy expenditure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four weeks of electrical stimulation improves glucose tolerance in a sedentary overweight or obese Hispanic population. Galvan, MJ., Sanchez, MJ., McAinch, AJ., et al.[2022]

A systematic review of 35 studies, including a meta-analysis of 9 randomized controlled trials with 180 participants, found that neuromuscular electrical stimulation (NMES) significantly lowers fasting blood glucose levels, indicating its effectiveness in improving glycemic control, especially in middle-aged and elderly individuals with type 2 diabetes and obesity.

The results suggest that NMES could be a beneficial therapeutic strategy for enhancing glycemic control in populations with physical impairments or metabolic disorders, although the protocols used in the studies varied and need standardization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of neuromuscular electrical stimulation on glycemic control: a systematic review and meta-analysis. Sanchez, MJ., Mossayebi, A., Sigaroodi, S., et al.[2023]

In a study involving 23 mice, neuromuscular electrical stimulation (NMES) significantly increased muscle mass compared to a sham treatment, indicating its potential to reverse muscle wasting in chronic disease.

NMES also improved insulin sensitivity, as shown by lower blood glucose levels during an insulin tolerance test, suggesting that NMES could have beneficial effects on metabolic health in patients with chronic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic neuromuscular electrical stimulation improves muscle mass and insulin sensitivity in a mouse model. Lotri-Koffi, A., Pauly, M., Lemarié, E., et al.[2021]

In a study involving 8 individuals with type 2 diabetes, low-frequency neuromuscular electrical stimulation (NMES) significantly reduced glucose levels after a glucose load compared to control conditions, indicating its potential efficacy in managing blood sugar levels.

The results also showed a strong positive correlation between the intensity of NMES and the reduction in blood glucose, suggesting that higher stimulation intensity may enhance glucose uptake in individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Low Frequency Neuromuscular Electrical Stimulation on Glucose Profile of Persons with Type 2 Diabetes: A Pilot Study. Jabbour, G., Belliveau, L., Probizanski, D., et al.[2018]

In a study involving 9 healthy men, neuromuscular electrical stimulation (NMES) at a self-selected comfortable intensity significantly increased energy expenditure (221 kcal) and carbohydrate oxidation compared to sitting still (159 kcal).

NMES also resulted in lower postprandial insulin levels, indicating potential benefits for metabolic health, making it a promising strategy for improving metabolic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of neuromuscular electrical stimulation on energy expenditure and postprandial metabolism in healthy men. Chen, YC., Davies, RG., Hengist, A., et al.[2021]

Neuromuscular electrical stimulation (NMES) can effectively retrain muscles and improve strength, particularly in the quadriceps, by adjusting parameters like pulse duration (400 to 600 μs) and pulse frequency (30 to 50 Hz) to optimize torque production while minimizing discomfort and fatigue.

Clinicians should consider optimal electrode placement and conditioning programs to further enhance the effectiveness of NMES, ensuring better patient outcomes during rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can the Use of Neuromuscular Electrical Stimulation Be Improved to Optimize Quadriceps Strengthening? Glaviano, NR., Saliba, S.[2019]

In a study involving 10 adults, neuromuscular electrical stimulation (NMES) with a 200-microsecond pulse duration allowed participants to tolerate significantly greater muscle torques compared to a 50-microsecond pulse duration, indicating enhanced efficacy for muscle strengthening.

The findings suggest that medium pulse durations may be more effective for maximizing muscle torque responses, despite the common belief that shorter pulses are preferable due to lower pain thresholds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of maximum tolerated muscle torques produced by 2 pulse durations. Scott, WB., Causey, JB., Marshall, TL.[2014]

Neuromuscular electrical stimulation (NMES) may fail to elicit muscle responses due to underlying peripheral nerve damage, as demonstrated in two case studies involving patients with unexpected neuropathies.

Simple reaction of degeneration (R/D) tests can effectively identify nerve lesions, guiding further diagnostic evaluations for patients experiencing significant muscle weakness or paralysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilizing the reaction of degeneration test for individuals with focal paralysis. Holland, TJ.[2021]

Insulin resistance (IR) primarily affects the body's ability to take up glucose, but it is also linked to a broader range of metabolic disorders, including type 2 diabetes and heart disease, especially in the context of rising obesity rates.

The review discusses the causes and clinical implications of IR, highlighting its significance in the management of various metabolic conditions and the need for effective treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin resistance syndrome. A review. Vasudevan, AR., Garber, AJ.[2017]

Insulin resistance is a major issue in 85-95% of patients with non-insulin-dependent diabetes mellitus (NIDDM), primarily influenced by genetic factors, obesity, and lack of exercise.

Regular exercise can improve muscle metabolism, helping to counteract the early defects in glycogen storage and fat oxidation seen in individuals at risk for NIDDM, and it can also prevent the progression to full-blown diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Interrelation of visceral fat and muscle mass in non insulin-dependent diabetes (type II): practical implications]. Brun, JF., Bringer, J., Raynaud, E., et al.[2006]

Insulin resistance, a key feature of obesity and type 2 diabetes, is influenced by both genetic and environmental factors, with physical inactivity being a significant contributor.

Exercise training improves mitochondrial function in skeletal muscle, making it an effective strategy for preventing and treating obesity and type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Physical exercise and insulin resistance: from muscle metabolic physiopathology to therapeutics]. Bordenave, S., Aguer, C., Kitzmann, M., et al.[2019]

Obese mice show insulin resistance in skeletal muscle due to a decrease in insulin receptors and alterations beyond the receptor level, leading to impaired glucose transport and reduced glycogen synthesis.

Serum from a patient with insulin resistance contains antibodies that inhibit insulin binding and mimic insulin effects, but it is less effective than insulin in stimulating glycogen synthesis, indicating different mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Studies of insulin insensitivity in soleus muscles of obese mice. Le Marchand-Brustel, Y., Freychet, P.[2019]

Insulin action involves several key biochemical events, including receptor autophosphorylation and glucose transporter translocation, which ultimately increase glucose transport and stimulate metabolic processes like glycogen synthesis.

In conditions like insulin resistance, such as obesity and type 2 diabetes, the primary issue is often the impaired transport of glucose into muscle tissues, with more severe cases also showing defects in insulin signaling beyond the receptor level.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin receptors and action in clinical disorders of carbohydrate tolerance. Pollet, RJ.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Four weeks of electrical stimulation improves glucose tolerance in a sedentary overweight or obese Hispanic population. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of neuromuscular electrical stimulation on glycemic control: a systematic review and meta-analysis. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Chronic neuromuscular electrical stimulation improves muscle mass and insulin sensitivity in a mouse model. [2021]

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

Effect of Low Frequency Neuromuscular Electrical Stimulation on Glucose Profile of Persons with Type 2 Diabetes: A Pilot Study. [2018]

5. Canada pubmed.ncbi.nlm.nih.gov

Effects of neuromuscular electrical stimulation on energy expenditure and postprandial metabolism in healthy men. [2021]

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

Can the Use of Neuromuscular Electrical Stimulation Be Improved to Optimize Quadriceps Strengthening? [2019]

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

Comparison of maximum tolerated muscle torques produced by 2 pulse durations. [2014]

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

Utilizing the reaction of degeneration test for individuals with focal paralysis. [2021]

9. Italy pubmed.ncbi.nlm.nih.gov

Insulin resistance syndrome. A review. [2017]

10. France pubmed.ncbi.nlm.nih.gov

[Interrelation of visceral fat and muscle mass in non insulin-dependent diabetes (type II): practical implications]. [2006]

11. France pubmed.ncbi.nlm.nih.gov

[Physical exercise and insulin resistance: from muscle metabolic physiopathology to therapeutics]. [2019]

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

Studies of insulin insensitivity in soleus muscles of obese mice. [2019]

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

Insulin receptors and action in clinical disorders of carbohydrate tolerance. [2019]