A Research Protocol: Comparison of Ultrasound Therapy with Zingiber Cassumunar Roxb based Phonophoresis and Conventional Gel in Patients with Knee Osteoarthritis-Randomized Control Trial

Background: Knee Osteoarthritis is considered as the leading cause of the disability in almost all over the world after age of 40. Almost about 54 percent people will end up in knee osteoarthritis in old age. Awareness of non-pharmacological treatment for knee osteoarthritis is more in practice in European as well as in Asian countries. Physical therapy, Ultrasound therapy, Otago exercises etc. are the treatments that are available for conservative management as well as preventive measure of knee Osteoarthritis. Methodology: Subjects with knee osteoarthritis with grade II to III on Kallgren and Lawrence classification will be included in the study N = 52. Two groups each of 26 will be allocated randomly as group A who will receive ultrasound treatment with Otago exercises control group and group B who will receive ultrasound treatment with zingiber Cassumunar based gel and Otago exercises as experimental group. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC), VAS, star excursion balance test will be performed before and after the treatment after 2 weeks with single blind procedure. Study Protocol Joshi and Phansopkar; JPRI, 33(46A): 15-21, 2021; Article no.JPRI.74525 16 Objective: This research will examine the effect of treatment with Zingiber Cassumunar based gel applied by means of phonophoresis with ultrasound therapy in knee osteoarthritis patients with Randomized control trial.


INTRODUCTION
Knee complex is a combination of patellofemoral and tibiofemoral articulations, that together gives three degrees of freedom to the knee and forms a synovial hinged joint. The medial and lateral menisci along with ligaments and muscles in and around the knee complex are responsible for the static and dynamic stability of the knee complex [1].
Knee joint complex is a major lower limb weight bearing joint which is constantly subjected to high pressure and is therefore susceptible to injuries [2]. These injuries if untreated later lead to degenerative changes in the bones that articulate to form the knee complex [3]. These degenerative changes lead to the condition termed as Osteoarthritis of knee which contributes to one of the most disabling conditions in the world. Since the condition is associated with forces and weight to which the joint is subjected to [3] , increase in the overall prevalence of obese individuals in population lead to the and increase in the prevalence of people suffering from Knee Osteoarthritis (KOA) [4].
Limited range of motion and stiffness due to pain, joint effusion and bony enlargements is the major manifestation of the condition [5]. As a result of these symptoms functional independence of the individual reduces. Surgical treatment for grade 4 of KOA or pain leading to severe functional dependency along with pharmacological treatment have long term side effects [6]. Researches have focused upon alternative approach for the long-term treatment of KOA. Exercises, rehabilitation and modifications of lifestyle are the most effective form of intervention according to the recent evidences [7]. Rehabilitation of KOA includes strength training of the lower limbs, proprioception training along with other stability exercises [8]. The condition generally affects the individuals in the geriatric age where the risk of injuries due to fall is also higher. Inclusion of exercises focusing on stability both static and dynamic in the rehabilitation is important to address the problem of fall which is a associated risk along with high dependency in KOA [9].
Otago Exercise programme is a set of exercises that include stretching, strengthening and balance exercises. Initially developed for the geriatric population to reduce the risk of fall, these when performed regularly are helpful in all the domains of rehabilitation of KOA [10].
Rehabilitation begins with reducing pain by application of therapeutic ultrasound by the physical therapist. The piezo electric effect generated by the high frequency of ultrasound results in an increase in the flow of blood thereby facilitating tissue recovery and reduction in inflammation and pain [11].
Natural Ayurvedic agents have anti -inflammatory effect and reduces pain in patients with Osteoarthritis of knee by its topical application. These Ayurvedic medicines do not generally have any side effects and are as well cost effect with high availability. No previous study has been done with the use of Zingiber Cassumunar Roxb in gel form [12]. There is lack of evidence on effectiveness of Zingiber Cassumunar Roxb as a coupling medium adjunct to routinely used aquasonic in phonophoresis. We use Zingiber Cassumunar Roxb. (dry Ginger) as the Ayurvedic herb with anti-inflammatory properties in the form of the gel. We therefore aim to study the effectiveness of this Zinger Cassumunar Roxb phonophoresis as a non-invasive alternative treatment for development of more effective modality with minimal side effects and lower costs [13].

Study Design
This study will be carried out in the OPD setting of Ravi Nair Physiotherapy College and AVBRH, Sawangi (Meghe), Wardha, All participants will be educated about the details of the intervention, research and data confidentiality prior to the start of the study. Those participants who will satisfy the inclusion criterion will have to sign an informed consent before participation. Those (n = 52) who full fill the inclusion criteria will then be included in the study for a duration of 2 weeks.

Trial Desig
In this single blinded controlled trial subjects in group A and group B were randomized by simple random sampling through envelope technique. Conventional therapy will be given to group A while group B will be experimental.

Inclusion Criteria
Participants aged between 40-60 years of all genders with unilateral knee Osteoarthritis having Stiffness < 30mins will be used as a reference population. The grade of osteoarthritis should be between 1-3 of OA of knee diagnosed in X-ray according to Kallgren and Lawrence classification.

Exclusion Criteria
Patients with Grade of OA 4 according to Kallgren and Lawrence classification having with or without any superficial and deep sensory impairments will not be chosen. Patients who have undergone total hip joint replacement (THR) or with clinically diagnosed neurological disorders like stroke, Parkinsonism and those with current participation in another OA intervention study will also be excluded. Those with severe physical disabilities (i.e., unable to walk even with a walking aid) or who are unable to comprehend are also not included in the study.

Recruitment Procedure
Patients who come to the OPD of RNPC and AVBRH who will meet the eligibility requirements according to the inclusion criteria and willing to participate will be engaged in the RCT.

Sample Size Consideration
The prevalence was referred from the research conducted by Venkatachalam J et al [12]. In power calculation, we calculated the total sample size required as 52 with number of participants within each group to be 26 with 95% confidence interval, and 0.10 desired error of margin.

Randomization
Participants after base line evaluation , who fulfill the inclusion criteria will then randomised into either of the group.A computer-generated randomisation schedule in randomized permuted blocks will be prepared by an independent statistician, to ensure the number of subjects undergoing the two treatments within each group are closely balanced and the allocation numbers will be placed in invisible sealed envelopes. These envelopes will be made available to the player after signing the consent form.

INTERVENTION DESIGN
Participants will receive the protocol 5 times a week for 2 weeks. An Assessment form is filled prior to administration of the intervention which includes the demographic data and the pretreatment values of our outcome measures for assessing pain, range of motion, functional disability and balance.

Group A (Control group)
The carefully monitored physiotherapy program will include 8 mins of continuous mode Ultrasound therapy of 1 MHz frequency with routine aqua sonic gel and at intensity of 0.8-2.5 w/cm 2 . This is then followed by Otago exercise program [14].

Group B (Experimental Group)
The carefully monitored physiotherapy program will include 8 mins of continuous mode Ultrasound therapy of 1 MHz frequency with Zingiber Cassumunar Roxb phonophoresis and an intensity of 0.8-2.5 w/cm 2 . This is then followed by Otago exercise program [15].

OUTCOME MEASURES
The primary outcome measure is Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for assessing functions. Visual Analogue Scale for pain [15,16], Universal goniometer to measure ranges and star excursion balance test (SEBT) a dynamic balance test, are secondary outcome requires flexibility strength and proprioception. SEBT is performed on eight lines taped to the ground, each of them at a 45-degree angle to on another leading to formation of a Star. The distance is marked in centimetres on the tape to determine the reach distance. The participant stands in the centre of this star and with the opposite leg are asked to reach as far as possible in the specified direction [17].

Data Management
Data of the study will be stored in a safe, secured store room with limited access for later review by a biostatistician, a researcher in charge.

Statistical Analysis
Statistical analysis will be done by using descriptive and interferential statistics using chi-snare and 2-test for the difference between two means. The software used in analysis will be SPSS 24.0 V and Graphed Prism 7.0 v with p < 0.05 considered as level of significance.

DISCUSSION
This research protocol is based on evaluation of pain, available movements, functions and dynamic balance post application of therapeutic Total Sample (N=52) Subjects will be screened by inclusion and exclusion criteria and consent with medical history will be obtained from them Statistical Analysis modality and a regular exercise regime at the end of 10 treatment sessions in subjects with osteoarthritis of knee (KOA) [18]. Therapeutic ultrasound is a modality proven to show positive outcomes in arthritic knee pain and swelling. This therefore remains as a conventional treatment approach in this single blinded randomized control trial for the control group [17]. . Newberry et al concluded that treatment modalities like TENS, whole body vibration are also an effective treatment approach with an optimal improvement in pain scores and functional ability of patients [12].
Phonophoresis, a technique to provide more effective therapeutic ultrasound have shown to decrease pain and improve functions significantly with the usage of drugs lidocaine [21]. Phonophoresis of Zingiber Cassumunar (Ginger) an easily available non pharmacological agent, a study previously not done in patients with KOA, will be carried out to assess its effectiveness supplemented with Otago Exercise programmes that have proven to be effective for strengthening of lower limbs as well as in enhancing balance in elderly adults.

CONCLUSION
The conclusion will be drawn from the analysis of the values obtained for the outcome measures post data collection.

DISSEMENATION AND PROTOCOL AMENDMENTS
The primary RCT findings will be sent to a foreign peer-reviewed journal for publication, regardless of whether the findings are positive, negative or inconclusive about the research hypothesis.

CONSENT
An informed consent will be obtained from the patient on a printed form with the signatures and will be given the proof of confidentiality.

ETHICAL APPROVAL
The Research Protocol was approved by Institutional Ethical Committee. We have Registered with the Clinical Trial Registry of India (CTRI) with REF NO. 2021/04/043216. The trial will be performed in accordance with the Declaration of Helsinki.

CONFIDENTIALITY
Specific Subject information will be kept separate from the central dataset, and will not be exchanged. All personal data will be stored securely before, during and after to preserve the confidentiality.