Efficacy of a Tailored COMET Protocol Combined with Medication on Vibratory Perception and SkinConductance in Diabetic Neuropathy- A Protocol for Randomized Controlled Trial

Introduction

These days, diabetes is thought to be one of the main causes of morbidity and death.¹ The International Diabetes Federation has released updated statistics showing that 463 million people worldwide have diabetes and 374 million are at risk of becoming type 2 diabetes mellitus (T2DM).² In India, the number of individuals with diabetes is expected to increase from approximately 77 million in 2019 to 134.2 million by 2045.² Numerous issues, such as microvascular and macrovascular consequences, are brought on by diabetes.^3–5

Diabetic neuropathy is the most prevalent and alarming consequence of diabetes mellitus (DM). Peripheral, focal, proximal, or autonomic can all be described. Over 40 million diabetics worldwide suffer from neuropathy.⁶ Diabetic peripheral neuropathy (DPN) is defined by the American Diabetes Association (ADA) as “the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes.⁷ It affects particular nerve system regions⁸ causing morbidity and raising the cost of diabetic care.⁹ Up to 50% of instances of this long-term diabetic consequence are asymptomatic.^10,11 Additionally, 40–60% of amputations of the lower extremities are caused by it.¹²

DPN symptoms might be silent and go unnoticed, or they can be subjective and transient,¹³ resembling symptoms of other illnesses. It may result in extremely painful symptoms or loss of feeling.¹⁴ Consequently, the preferred technique for diagnosing peripheral neuropathy is clinical examination.¹⁵ Significant abnormalities in touch and pain sensitivity, kinaesthesia, lower-limb proprioception, and vibration sense are common symptoms of diabetic peripheral neuropathy (DPN), which is brought on by the stimulation of neuronal death and restriction of nerve regeneration.¹⁶ Sensory alterations in the “glove-and-stocking” distribution are the primary indicator of it.¹⁷

We don’t know the actual prevalence of DPN. According to studies, the percentage of diabetes patients with neuropathy can range from 10% to 90%, depending on the definition and techniques employed. In surveys of Indian patients, DPN has been reported in 26–31% of cases.¹⁸ DPN is difficult to treat, and there are few medications available. Tricyclic antidepressants, opioids, gabapentin, pregabalin, serotonin and norepinephrine reuptake inhibitors, and gabapentin are common therapy drugs.¹⁹

Frequent exercise lowers body weight enhances insulin sensitivity and blood glucose control, and lowers the risk of neuropathy in diabetic individuals. The standard treatment for obesity and diabetes mellitus involves nutrition and increased physical activity.²⁰ Research suggests that those with type 1 diabetes are more likely than those with other types of diabetes to exercise. The data demonstrates that practice interventions can enhance diabetes control. The majority of research have shown that it is beneficial to carry out training treatments between 8 weeks and 12 months for diabetes patients who have a peripheral neuropathy risk factor for diabetic foot ulcers. Significant increases in physical activity have been observed in several investigations, without a corresponding rise in injury risk. If health care is incomplete, foot ulcers may develop, which is the most common cause of hospitalization and amputation.²¹ Usually, the combination of various treatments, including pharmacotherapy, physiotherapy, and orthotic devices are used to maintain biomechanical parameters, physiological patterns, and at last, for wound healing.²²

Insulin therapy, including pharmacotherapy and lifestyle interventions, is considered a conventional treatment for preventing diabetes complaints.²³

Participant timeline

Data will be collected on the baseline as pre and post-data, followed by intervention for 4 weeks and post-intervention data on the last day of the 4^th week is again recorded, CONSORT Flow chart is mentioned in Figure 1.

Figure 1. CONSORT flow chart.

Group A: The experimental group will be receiving COMET protocol (Table 1), the Acronym

• 1. COntrast Bath

• 2. Mobility - Nerve Mobilization & Mobility Exercises

• 3. E-Stim - Plantar Electrical Stimulation

• 4. Therapeutic Foot Massage

Table 1. COMET protocol.

S. No.	Intervention	Procedure	Dosage
1.	Contrast Bath	Application of Hot & Cold Immersion: 1. Position of the Patient: The patient is comfortably placed in a seated position on a chair with back support. The height of the chair must be sufficient to position the hips and knees at 90o. 2. Instructions to the Patient: The patient is instructed to be as relaxed as possible and inform the therapist at once in case of any discomfort. 3. Procedure: i. The contrast bath is applied either by a Contrast Bath Modality (CBM) or by using a bucket filled with warm or cold water sufficient to immerse the patient’s foot. ii. A thermometer is used to record the water temperature throughout the intervention and a clock to measure the time duration. iii. The patient is instructed to place his foot (one at a time) in the CBM/Bucket filled with warm water between 37o-43o for a duration of 4 minutes. iv. After 4 minutes, the leg is lifted from the bucket and at once placed in a CBM/Bucket filled with cold water between 12o-15o for a duration of 1 minute. v. This process of alternating between warm water and cold water is repeated 4 times for a total duration of 20 minutes. 4. Winding up of the procedure: Once the total immersion time of 20 minutes is complete, the patient is instructed to lift his leg from the bucket, and the skin is dried with a soft towel. The process is repeated for the contralateral foot.	20 minutes per session, 6 sessions per week for 4 weeks
2.	Nerve Mobilization	Application of Nerve Mobilization to Posterior Tibial and Peroneal nerve. 1. Position of the Patient: The patient is positioned in a relaxed supine lying position without any pillow under the head. 2. Instructions to the Patient: The patient is instructed to be as relaxed as possible and inform the therapist at once in case of any discomfort. 3. Nerve mobilization for Peroneal Nerve: Application of Proximal and Distal Sliders: i. With the patient in a supine, and the therapist in a walk stance on the side being treated, the therapist elevates the hip to 45o and the knee slightly flexed to allow the leg to be positioned horizontally. ii. The therapist faces towards the foot and holds the knee between his forearm and trunk. The therapist's upper limb nearer to the patient will support the leg. iii. The volar aspect of the therapist's forearm will be in contact with the posteromedial aspect of the patient's leg supporting it. iv. The farther upper limb of the therapist places his palm on the dorsolateral aspect of the patient's forefoot such that the fingers overlap the toes, and the thumb is towards the dorso- medial surface. v. For the proximal slider, the therapist extends the knee on the flexed hip with the foot drawn into dorsiflexion and eversion. vi. For the distal slider, the therapist flexes the knee up to 90o on the flexed hip with the foot drawn into plantarflexion and inversion. 4. Nerve mobilization for Posterior Tibial Nerve: Application of Proximal and Distal Sliders: i. With the patient in a supine, and the therapist in a walk stance on the side being treated, the therapist elevates the hip to 45o and the knee slightly flexed to allow the leg to be positioned horizontally. ii. The therapist faces towards the foot and holds the knee between his forearm and trunk. The therapist's upper limb nearer to the patient will support the leg. iii. The volar aspect of the therapist's forearm will be in contact with the posteromedial aspect of the patient's leg and the therapist's hand will caress the calcaneum of the patient. iv. For the proximal slider, the therapist dorsiflexes the heel with his proximal hand by pushing it forward and dorsiflexes the forefoot and toes drawing them into eversion with his distal hand. This is done till resistance is encountered or symptoms elicited. v. This is followed by slowly extending the knee until further range is impossible or there is discomfort. vi. At this position, the pressure of dorsiflexion and eversion is slowly released with the knee still in the previous extended position. This will allow the nerve to migrate proximally. vii. For the distal slider, the therapist elevates the hip to 45o and the knee slightly flexed to allow the leg to be positioned horizontally. viii. The therapist dorsiflexes the heel with his proximal hand by pushing it forward and dorsiflexes the forefoot and toes drawing them into eversion with his distal hand. This is done till resistance is encountered or symptoms elicited.	Once a good response becomes consistent, each movement can be performed in four or five sets of 5-30 repetitions per set (maximum of 25-150 repetitions depending on the severity of symptoms and response). Breaks of approximately 10 seconds to several minutes between sets can be given according to the patient outcome. Total Treatment time between 10-15 minutes per session, 3 sessions per week for 4 weeks.
3.	Mobility Exercise	Application of an Aerobic Mobility Exercise: The patient will be instructed to enrol in a walking program initiating with 5 minutes of normal walking for warm-up, followed by 40 minutes of brisk walking at their favourable pace, and ending with 5 minutes of normal walking for cool down.	Total of 50 minutes per day, 300 minutes per week for 4 weeks
4.	Plantar Electrical Stimulation	Application of Transcutaneous Electrical Nerve Stimulation on the plantar surface of the foot: 1. Position of the Patient: The patient is comfortably placed in a supine position with a pillow under the knee. 2. Instructions to the Patient: The patient is instructed to be as relaxed as possible and is informed that he will feel mild tingling in the sole where the electrode is placed. The patient is also instructed to inform the therapist immediately in case of discomfort. 3. Procedure: i. The skin on the plantar surface of both feet is cleansed with cotton dipped in tap water and dried. ii. A two-channel TENS machine is used with each channel of paired electrodes applied on each foot. iii. The self-sticking adhesive electrodes are used, and each pair are placed with one electrode over the metatarsal heads in the middle of the forefoot and the other over the attachment of the plantar fascia in the middle of the junction between the mid-foot and hind foot. iv. The machine is switched on, and the intensity is gradually increased till the patient informs a comfortable tingling sensation under the electrodes. v. The intensity is maintained at this level and the foot is stimulated for a duration of 20 minutes. 4. Winding up of the procedure: Once the total stimulation time of 20 minutes is complete, the machine is switched off, the electrodes are removed, and the skin is inspected for any changes. If no changes are found, the skin is cleansed again with cotton dipped in tap water and dried. The patient is instructed to get up from a lying position whenever he/she is comfortable.	20 min at 80Hz, 60μs pulse duration. Comfortable tingling, 3 times per week for 4 weeks
5.	Therapeutic Foot Massage	Application of Therapeutic Foot Massage Techniques: 1. Position of the Patient: The patient is comfortably placed in the prone position and the lower limb is exposed up to the inferior gluteal region. 2. Instruction to the patient: The patient is instructed to be relaxed as much as possible and inform the therapist at once in case of any discomfort. 3. The procedure of Massage: i. Massaging gel or coconut oil is used for massaging as it helps in moisturizing and lubrication. ii. The massage begins with touching the heel of the foot to initiate contact. iii. Effleurage strokes are used from the heel to the entire leg 3-5 times to spread the lubricant and warm the tissues. iv. Petrissage manipulation including horizontal and vertical thumb and finger kneading, and static pressure are applied to the bottom of the feet starting with the base of the middle toe, moving one thumb width up towards the center of the foot, moving up towards the heel, spreading down towards the mid arches of the foot and ending at the base of the first and fifth toes. v. These are followed by effleurage strokes 3-5 times toward the popliteal lymph nodes. vi. Using both hands, hold the calcaneum between the thenar and hypothenar muscles and apply compression and distraction at the talocalcaneal joint. vii. This is followed by contacting the Achilles tendon by the ulnar side of both hands caressing it and sliding back and forth. viii. The calf muscle is reached with hands still in contact with the skin, and petrissage manipulations including thumb kneading, finger kneading, wringing, and picking up are applied to the calf muscles from distal to proximal till the knee joint line. ix. Thumb kneading is done to the tender areas of the calf muscle between the heel and the knee joint. x. These manipulations are ended by effleuraging the entire foot, leg, and thigh 3-5 times. 4. Winding of the Procedure: After completion of the massage, the patient is instructed to lie for a few minutes and get up whenever he/she is comfortable.	10-15 minutes per session, 3 times per week for 4 weeks

Group B The control group will be receiving their medication for diabetic polyneuropathy and general exercises will be taught which the participants will be continuing for a month.

Methods

Data collection methods: The assessment and collection of outcomes will be done in the preintervention stage after assigning them to the intervention groups. Post- intervention data will be collected on the same day. This will be followed by the collection of post-intervention data after the completion of 4 weeks of intervention.

Data management: The collected information will be summarized by using frequency percentage for qualitative data and mean and standard deviation for quantitative data.

Statistical methods: To find the effectiveness of COMET Protocol along with medication on Vibratory Perception Threshold (VPT), Galvanic Skin Conductance (GSC), Michigan Neuropathy Screening Instrument (MNSI) and NeuroQOL in subjects with Diabetic Polyneuropathy, paired t-test will be used for within-group comparison and unpaired t-test will be used for between-group comparisons. If the data is not following a normal distribution, the Wilcoxon sign rank test will be used for within-group comparisons and the Mann-Whitney U test will be used for between- group comparisons.

A “p” value less than 0.05 will be considered significant. Outcome measures will be evaluated by using SPSS 21 software version.

Discussion

With a specific focus on vibratory perception and skin conductance as primary outcome measures, this proposed randomized controlled trial seeks to assess the effectiveness of a customized COMET protocol in conjunction with medication for the management of diabetic neuropathy. A thorough evaluation of participants’ baseline skin conductance and vibratory perception will be part of the procedure. After that, participants will be randomly assigned to either the intervention group, which will get the customized COMET protocol and the control group, which will receive standard medication alone. Using established measurement instruments, researchers will closely monitor changes in skin conductance and vibratory perception throughout the experiment to provide quantitative evidence on the efficacy of the combined intervention approach. The research will comply with strict ethical standards and give top priority to participant safety, guaranteeing that every participant will receive the necessary attention and supervision throughout the study. This trial has the potential to offer important insights into the comprehensive management of diabetic neuropathy by examining the effects of the customized COMET protocol in conjunction with medication on vibratory perception and skin conductance. Ultimately, this could improve the quality of life for those who suffer from this difficult condition.

This study protocol aims to produce credible evidence on the efficacy of the customized COMET protocol combined with medication in addressing vibratory perception and skin conductance in diabetic neuropathy through the use of a robust randomized controlled trial design and standardized assessment tools. The study will carefully gather and examine data pertaining to alterations in these physiological parameters, allowing for a thorough assessment of the influence of the intervention on peripheral nerve function and autonomic nervous system activity. The trial design places a strong emphasis on participant welfare and ethical considerations, making sure that participants receive the proper assistance and oversight during the study. Through a more thorough comprehension of the possible advantages of the customized COMET protocol when combined with medication, this study could influence clinical practice and help create efficient, individualized treatment plans for people with diabetic neuropathy, ultimately improving their general health and well-being.