Combined Application of Electrical Stimulated Antagonist Contraction During Walking (Walking Study)
Condition: Knee Osteoarthritis
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Study type: Interventional

Summary: 
      Osteoarthritis of the knee (KOA) is the most common cause of disability in older adults.
      Osteoarthritis involves a loss of cartilage, which acts like a cushion between the bones as
      well as changes in the bones of joints. Once the joint cartilage is gone, the body does not
      produce new cartilage. Joint damage can contribute to pain. Currently, treatment for pain
      associated with knee osteoarthritis includes exercise. However, exercise at a medium- to
      high-intensity level can be problematic for people with knee pain. Because exercise is a
      common treatment for knee pain but many people experience pain during exercise, researchers
      hope to find a safer and more effective exercise method to strengthen the muscles around the
      knee.

      Both aerobic exercise and resistance exercise are recommended for the treatment of people
      with knee pain. However, pain can be a barrier to participating in exercise at a moderate or
      vigorous intensity. Electrical stimulation of muscles holds potential to allow effective
      exercise to be completed at tolerable intensities. Transcutaneous electrical nerve
      stimulation (TENS) is the use of very low electric currents produced by a device to stimulate
      the nerves, to treat pain. Neuromuscular electrical stimulation (NMES) uses low electrical
      current to cause muscles to contract.

      By doing this study, the investigators hope to learn if a hybrid training system (HTS), using
      a combination of NMES and walking, is effective in strengthening muscles in people with knee
      pain, aching or stiffness.

      In this pilot study, the investigators will use walking with TENS as conventional exercise.

      Randomized controlled trial will be conducted to compare the effect of walking augmented by
      HTS with walking without HTS. The investigators will evaluate the relative advantages of
      training that combines HTS with conventional walking exercise on the improvement of muscle
      strength, physical function, and pain relief in obese women with frequent knee symptoms.

      Study Hypotheses: Compared with walking with sensory TENS, walking with HTS will:

        -  1 increase quadriceps muscle strength.

        -  2 decrease knee pain.

      Exploratory Hypotheses:

        -  3 improve physical function.

        -  4 increase PPT (improve central sensitization).

        -  5 improve self-reported quality of life.
    

Detailed description: 
      Osteoarthritis of the knee (KOA) is the most common cause of disability not only in the
      United States but also in Japan. KOA is associated with pain, quadriceps weakness, swelling,
      instability, decline of range of motion, physical function, and quality of life (QOL) (1). In
      particular, quadriceps weakness may contribute to incident symptomatic and progressive
      disease (2, 3), cause functional limitations and disability (4) and increase the risk of
      mortality (5). Both aerobic exercise and resistance exercise are recommended for the
      treatment of people with knee osteoarthritis (KOA) (6). However, exercise at a moderate or
      severe intensity is often a problem for people with knee pain or a history of knee injury.

      Neuromuscular electrical stimulation (NMES) is widely used as a method to increase muscle
      strength and improve physical function even at a low-moderate exercise intensity (7).
      However, NMES effect may prove to be insufficient because the exercise intensity is
      determined by the electrical stimulation endurance level of the user (7). On the other hand,
      transcutaneous electrical stimulation, so-called transcutaneous electrical nerve stimulation
      (TENS), is effective for pain relief (8). Knee pain independently reduced quadriceps strength
      and activation (9). TENS restores inhibited quadriceps motor function (central and muscle
      activation) through pain relief (10). Moreover the combined application of electrical
      stimulation (ES) and volitional contractions (VC) is said to be more effective than ES or VC
      alone (11). Therefore, a hybrid training system (HTS) that resists the motion of a
      volitionally contracting agonist muscle using the force generated by its electrically
      stimulated antagonist (NMES) was developed as a way to combine the application of electrical
      stimulation and voluntary contraction (12). HTS is a method that eliminates the disadvantages
      of both volitional exercise and NMES (13). It has been reported that HTS is a new training
      technique that can increase both muscular strength and muscle mass (12, 13, 14, 15).
      Recently, HTS is showing promise as a countermeasure for the musculoskeletal disuse of
      astronauts because the HTS technique can generate exercise resistance within the body even if
      there is no gravity (1). In addition, HTS can be utilized during many different types of
      exercise (e.g. knee extension exercise, squat and hip flexion, walking exercise, and cycling
      exercise) (17, 18). It seems to be more effective for improvement of muscle strength and
      physical function to combine HTS with easy exercise (e.g. knee extension, walking, and
      squats) for KOA patients.

      The main purpose of exercise therapy for KOA is not only muscular strength improvement (the
      quadriceps femoris muscle in particular) and but also pain relief (19, 20). Muscular strength
      improvement protects joints and relieves nociceptive stimulation. However, exercise sometimes
      increases pain. In addition to the pathological change in articular structures, changes in
      central pain processing or central sensitization appear to be involved in KOA pain (19).
      Murphy et al. reported that 36% of a heterogenous sample of patients with hip and KOA
      demonstrated evidence of central sensitization (22). This finding has been incompletely
      characterized, but it is necessary to consider central sensitization in the treatment of
      patients with KOA. From a theoretical perspective, exercise has the potential to treat the
      process of central sensitization: e.g. exercise activates brain-orchestrated endogenous
      analgesia (23). An initial bout of high intensity eccentric exercise induces central
      sensitization, but a repeated round of exercise facilitates inherent protective spinal
      mechanisms (repeated bout effect) (24). Moreover, ipsilateral resistance exercise may
      possibly prevent the central sensitization (25). Therefore, a time-contingent approach which
      implies that the patient does not cease exercise bouts once local pain severity increases is
      recommended (22). A few reports about the dysfunctional endogenous analgesia for patients
      with musculoskeletal pain response to aerobic exercise were shown, but neither type of
      aerobic exercise was able to activate endogenous analgesia (24). At present, there is no
      report of an exercise method that is effective in central sensitization pain patients.
      Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophic family of growth
      factors. The loss of BDNF usually leads to neurodegeneration in these motor centers and
      eventually results in several severe motor diseases, such as amyotrophic lateral sclerosis,
      spinocerebellar ataxias, Parkinson's disease, Huntington's disease, as well as vestibular
      syndrome. These neurotrophic factors (e.g., decreasing brain-derived neurotrophic factor) are
      promising new avenues for diminishing hyperexcitability of the CNS in central sensitization
      pain patients (2). Da Graca-Tarrago et al. showed that a 30-minute electrical intramuscular
      stimulation in osteoarthritis decreased pain, increased the local pain pressure threshold
      (PPT), and decreased BDNF (27). Gajewska-Wozniak et al. reported that low-threshold
      electrical stimulation of peripheral nerves to stimulate Ia afferent fibers (proprioceptive
      signaling) might affect the expression of BDNF in rats (28). HTS is an exercise technique
      that uses electrically eccentric muscle contraction. Yamaguchi et al. showed that the soleus
      H-reflex increased after one HTS adversely in conventional resistance exercise (29). This
      seems to indicate that HTS serves to activate Ia fibers. HTS may affect central sensitization
      and relieve pain in KOA patients.
    

Intervention name(s): Hybrid Training System (HTS); Sensory TENS
Intervention type(s): Device; Device
Intervention description(s): Electrodes (15 cm x 6 cm) will be placed over the quadriceps and electrodes (11 cm x 6 cm) (Sekisui Plastics Co., Tokyo, Japan) will be placed over the hamstrings. Electrical stimulation parameters will be based on a standard Russian waveform in which a 5,000 Hz carrier frequency is modulated at 40 Hz (2.4 ms on, 22.6 ms off) to deliver a rectangular voltage biphasic pulse. Acceleration sensors as a joint motion sensor (EWTS9PD, Home Appliances Development Center Corporate Engineering Division, Appliances Company Panasonic Corporation 2-3-1-2 Noji-higashi,Kusatsu City, Shiga, Japan) is placed on the front of each leg 88mm above the patellar edge. It analyzes the algorithm of each exercise pattern, and stimulates the antagonist of the motion of each bilateral knee joint during exercise. Electrical stimulation intensity will be set to ~50-60% of 1RM based on the subject's tolerance. The subject's tolerance gradually increases, and electrical stimulation intensity is reset every 2 weeks.; The electrical stimulation intensity will be set under the muscle contraction threshold (but at a level at which the subject can perceive as sensory TENS). Electrical stimulation parameters (i.e. waveform and pulse duration) will be the same of HTS, while the amplitude will be lower. The subject will be stimulated using the same device as for HTS.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment