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Knee OsteoarthritisNCT02730598

Combined Application of Electrical Stimulated Antagonist Contraction During Walking (Walking Study)

A study testing Hybrid Training System (HTS) and Sensory TENS in people with Knee Osteoarthritis, run by University of Kansas Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 39 to 70 years, women only
Conditions the study is for
Knee Osteoarthritis
What is being tested?
Hybrid Training System (HTS) and Sensory TENS
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteUnited States
Study dates
Feb 2016to 20 Jan 2017
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 39 to 70 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Female
  • Age 40-70 years
  • Knee symptoms (pain, aching, or stiffness) on most of the last 30 days (categorically defined)
  • Body Mass Index (BMI) 30-45kg/m2

Who cannot join

  • Resistance training at any time in the last 3 months prior to the study
  • Bilateral knee replacement
  • Lower limb amputation
  • Lower limb surgery in the last 6 months that affects walking ability or ability to exercise
  • Back or hip problems that affect walking ability or ability to exercise
  • Unable to walk without a cane or walker
Show all 22Show fewer
  • Inflammatory joint or muscle disease such as rheumatoid or psoriatic arthritis or polymyalgia rheumatica
  • Multiple sclerosis or other neurodegenerative disorder
  • Known neuropathy
  • Currently being treated with insulin for diabetes
  • Currently being treated for cancer or having untreated cancer
  • Terminal illness (cannot be cured or adequately treated and there is a reasonable expectation of death in the near future)
  • Peripheral Vascular Disease
  • History of myocardial infarction or stroke in the last year
  • Chest pain during exercise or at rest
  • Use of supplemental oxygen
  • Inability to follow protocol (e.g. lack of ability to attend visits or understand instructions)
  • Staff concern for participant health (such as history of dizziness/faintness or current restrictions on activity)
  • Unable to attend more than 2 days within any 1 week or unable to attend 4 or more sessions during the study
  • Implanted cardiac pacemaker, spinal cord stimulator, baclofen or morphine pump or other implanted electrical device.
  • Dermatitis or skin sensitivity to tape used in the study.
  • Pregnancy

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

Other trials in United States

About this study

Official title: Determining Efficacy of the Combined Application of Electrical Stimulated Antagonist Contraction During Walking With Sensory TENS for Increasing Strength and Decreasing Pain in Women With Frequent Knee Symptoms

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.

Read more

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.
Read the 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.

Being tested
Hybrid Training System (HTS), Sensory TENS
Medical subject headings
Osteoarthritis, Knee

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hybrid Training System (HTS)Device

    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.

  • Sensory TENSDevice

    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.

Study groups in NCT02730598
Study groupRoleWhat they receive
Hybrid Training System (HTS)ExperimentalHTS stimulation while walking at a comfortable pace for 30 minutes.
Receives: Device: Hybrid Training System (HTS)
Transcutaneous Electrical Nerve Stimulation (TENS)Active comparatorSensory TENS while walking at a comfortable pace for 30 minutes.
Receives: Device: Sensory TENS

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Knee Extensor Strength Assessed by Isokinetic Dynamometer.

    Participants will be familiarized with strength testing equipment and counseled on proper lifting technique. They will undergo testing to determine their peak isokinetic knee extensor torque, using an isokinetic dynamometer.

    Measured: Baseline and 12-week follow-up

Secondary outcomes (7)
  1. Change in Knee Flexor Strength Assessed by Isokinetic Dynamometer

    Participants will be familiarized with strength testing equipment and counseled on proper lifting technique. They will undergo testing to determine their peak isokinetic knee flexor torque, using an isokinetic dynamometer.

    Measured: Baseline and 12-week follow-up

  2. Change in Knee Pain Assessed by a Visual Analog Scale (VAS)

    Knee pain will be evaluated using a visual analog scale (VAS) of 100 mm from no pain (0 mm) to the worst imaginable pain (100 mm). Participants will be asked to record their pain levels of the past one week.

    Measured: Baseline and 12-week follow-up

  3. Change in Knee Pain Assessed by Knee Injury and Osteoarthritis Outcome Score (KOOS)

    The Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscale was used at baseline and follow-up to assess participant outcomes. The pain subscale is made up of 9 questions and was scored from zero to 100, with zero corresponding to extreme knee problems and 100 corresponding to no knee problems.

    Measured: Baseline and 12-week follow-up

  4. Change in Quality of Life (QOL) Assessed by Knee Injury and Osteoarthritis Outcome Score (KOOS)

    The Knee Injury and Osteoarthritis Outcome Score (KOOS) Quality of Life (QOL) subscale was used at baseline and follow-up to assess participant outcomes. The QOL subscale is made up of 4 questions and was scored from zero to 100, with zero corresponding to extreme knee problems and 100 corresponding to no knee problems.

    Measured: Baseline and 12-week follow-up

  5. Change in 20-meter Walk Time.

    Average time of two trials used for each participant.

    Measured: Baseline and 12-week follow-up

  6. Change in 5-chair Stand Time.

    Average time of two trials used for each participant.

    Measured: Baseline and 12-week follow-up

  7. Change in Stair Climb Time.

    Average time of two trials used for each participant.

    Measured: Baseline and 12-week follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Apr 2016 (estimated)
  2. Study startFeb 2016
  3. Primary completion20 Jan 2017
  4. Study completion20 Jan 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02730598
Sponsor's protocol ID
STUDY00003435
Status last verified
Jun 2018
First submitted
1 Apr 2016
Last updated
15 Jun 2018
Data monitoring committee
No
Individual data sharing
No

Publications

  • Muraki S, Akune T, Oka H, En-yo Y, Yoshida M, Saika A, Suzuki T, Yoshida H, Ishibashi H, Tokimura F, Yamamoto S, Nakamura K, Kawaguchi H, Yoshimura N. Association of radiographic and symptomatic knee osteoarthritis with health-related quality of life in a population-based cohort study in Japan: the ROAD study. Osteoarthritis Cartilage. 2010 Sep;18(9):1227-34. doi: 10.1016/j.joca.2010.06.001. Epub 2010 Jul 13.

    PubMed 20633679
  • Segal NA, Glass NA, Felson DT, Hurley M, Yang M, Nevitt M, Lewis CE, Torner JC. Effect of quadriceps strength and proprioception on risk for knee osteoarthritis. Med Sci Sports Exerc. 2010 Nov;42(11):2081-8. doi: 10.1249/MSS.0b013e3181dd902e.

    PubMed 20351594
  • Segal NA, Glass NA, Torner J, Yang M, Felson DT, Sharma L, Nevitt M, Lewis CE. Quadriceps weakness predicts risk for knee joint space narrowing in women in the MOST cohort. Osteoarthritis Cartilage. 2010 Jun;18(6):769-75. doi: 10.1016/j.joca.2010.02.002. Epub 2010 Feb 11.

    PubMed 20188686
  • van Dijk GM, Dekker J, Veenhof C, van den Ende CH; Carpa Study Group. Course of functional status and pain in osteoarthritis of the hip or knee: a systematic review of the literature. Arthritis Rheum. 2006 Oct 15;55(5):779-85. doi: 10.1002/art.22244.

    PubMed 17013827
  • Nuesch E, Dieppe P, Reichenbach S, Williams S, Iff S, Juni P. All cause and disease specific mortality in patients with knee or hip osteoarthritis: population based cohort study. BMJ. 2011 Mar 8;342:d1165. doi: 10.1136/bmj.d1165.

    PubMed 21385807
  • Linda S Pescatello, Ross Arena, Deborah Riebe, Paul D Thompson. ACSM's Guidelines for Exercise Testing and Prescription by American College of Sports Medicine., 9nd ed., Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia, PA. 2014

  • Giggins O, Fullen B, Coughlan G. Neuromuscular electrical stimulation in the treatment of knee osteoarthritis: a systematic review and meta-analysis. Clin Rehabil. 2012 Oct;26(10):867-81. doi: 10.1177/0269215511431902. Epub 2012 Feb 9.

    PubMed 22324059
  • Rutjes AW, Nuesch E, Sterchi R, Kalichman L, Hendriks E, Osiri M, Brosseau L, Reichenbach S, Juni P. Transcutaneous electrostimulation for osteoarthritis of the knee. Cochrane Database Syst Rev. 2009 Oct 7;2009(4):CD002823. doi: 10.1002/14651858.CD002823.pub2.

    PubMed 19821296
  • Park J, Hopkins JT. Induced anterior knee pain immediately reduces involuntary and voluntary quadriceps activation. Clin J Sport Med. 2013 Jan;23(1):19-24. doi: 10.1097/JSM.0b013e3182717b7b.

    PubMed 23103783
  • Son SJ, Kim H, Seeley MK, Feland JB, Hopkins JT. Effects of transcutaneous electrical nerve stimulation on quadriceps function in individuals with experimental knee pain. Scand J Med Sci Sports. 2016 Sep;26(9):1080-90. doi: 10.1111/sms.12539. Epub 2015 Sep 8.

    PubMed 26346597
  • Paillard T. Combined application of neuromuscular electrical stimulation and voluntary muscular contractions. Sports Med. 2008;38(2):161-77. doi: 10.2165/00007256-200838020-00005.

    PubMed 18201117
  • Yanagi T, Shiba N, Maeda T, Iwasa K, Umezu Y, Tagawa Y, Matsuo S, Nagata K, Yamamoto T, Basford JR. Agonist contractions against electrically stimulated antagonists. Arch Phys Med Rehabil. 2003 Jun;84(6):843-8. doi: 10.1016/s0003-9993(02)04948-1.

    PubMed 12808536
  • Matsuse H, Shiba N, Umezu Y, Nago T, Tagawa Y, Kakuma T, Nagata K, Basford JR. Muscle training by means of combined electrical stimulation and volitional contraction. Aviat Space Environ Med. 2006 Jun;77(6):581-5.

    PubMed 16780234
  • Iwasaki T, Shiba N, Matsuse H, Nago T, Umezu Y, Tagawa Y, Nagata K, Basford JR. Improvement in knee extension strength through training by means of combined electrical stimulation and voluntary muscle contraction. Tohoku J Exp Med. 2006 May;209(1):33-40. doi: 10.1620/tjem.209.33.

    PubMed 16636520
  • Takano Y, Haneda Y, Maeda T, Sakai Y, Matsuse H, Kawaguchi T, Tagawa Y, Shiba N. Increasing muscle strength and mass of thigh in elderly people with the hybrid-training method of electrical stimulation and volitional contraction. Tohoku J Exp Med. 2010 May;221(1):77-85. doi: 10.1620/tjem.221.77.

    PubMed 20453461

Questions about this trial

What is this clinical trial studying?

A study testing Hybrid Training System (HTS) and Sensory TENS in people with Knee Osteoarthritis, run by University of Kansas Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Knee Extensor Strength Assessed by Isokinetic Dynamometer. (time frame: Baseline and 12-week follow-up). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02730598, which also lists 31 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2018.

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