Efficacy and safety of tablet Ligashot in patients with ligament injury of knee and shoulder

INTRODUCTION

Ligament of joints are responsible for connecting one bone to another and for controlling the range of motion within a joint. Traffic and sports-related accidents, involving high-energy and low-energy trauma respectively, are the primary causes cruciate ligament injuries.¹ Ligament injury of knee and shoulder accounts for 31% among adult population in India.² Grade 1 and 2 ligament injury treatment involves acute symptomatic treatment followed by 12 weeks of supervised physiotherapy, beginning with restoring a full range of motion.³ Ligashot Tablet is a nutraceutical, acting on the musculo-skeletal system of the body.

The active ingredients of Ligashot tab are chondroitin sulfate 200 mg, collagen peptide 150 mg, curcumin 100 mg, cyanocobalamin 1 µg, aflapin 100 mg, vitamin B6-1.4 mg, vitamin B12 0.001 mg, silica (Bambusa vulgaris)-7.5 mg, elemental iron 10 mg, glucosamine 250 mg, L-glutamic acid 50 mg, L-lysine 100 mg, manganese sulphate 1 mg, niacinamide 5 mg, proline 100 mg, quercetin 25 mg, vitamin C 35 mg and zinc sulphate 10 mg.

Low doses of glucosamine and chondroitin sulphate effectively stimulate collagen and non-collagenous protein (NCP) synthesis of ligament cells in vitro.⁴ Vitamin C functions as a potent antioxidant by neutralizing harmful reactive oxygen species (ROS), which cause cell apoptosis during the inflammatory phase.⁵ Bamboo silica extract is derived from the leaves and stem of the Bambusa vulgaris found in India.⁶ Curcumin extract’s analgesic and anti-inflammatory properties can aid in the post-operative healing of ligament injuries.⁷Aflapin obtained from Boswellia serrata gum resin. It reduces pain and improves physical function in inflammatory conditions of knee.⁸

Ligashot tablet efficacy in grade 1 and 2 ligament injury of knee and shoulder assessed by decrease in pain intensity at 12 weeks of treatment, changes in inflammatory parameters, improvement in MRI changes and improvement in QoL. Its safety assessed by adverse drug reactions and events during the study period. Many drugs are available in the market for treating symptoms of grade 1 and 2 ligament injury of knee and shoulder, but there is still need for drugs with least adverse effects. So, in this study, an attempt has been done with tablet Ligashot for treating symptoms of grade 1 and 2 ligament injury of knee and shoulder.

METHODS

The present study is an outcome, quasi-experimental study where patients with ligament injury of knee and shoulder, according to inclusion criteria were included and assessed after treatment. Patients were given tablet Ligashot daily for 3 months. Tablet Ligashot sponsored by Innovcare lifesciences Pvt Ltd, Mumbai. The study was done in Thirumalai Medical Centre and in Sri Ortho Care Clinic in Pondicherry during October 2023 to April 2024. The study was registered in clinical trial registry of India: CTRI/2023/09/057919. Independent ethics committee approval obtained for this study from ethique De La nature association in 19^th August 2023.

Inclusion criteria

Male or female patients aged more than 18 years with grade 1and 2 ligament injury of knee, shoulder-with or without dislocation, pain defined by a level of greater than or equal to 30 mm on a 100 mm VAS, patient who has not participated in any other clinical trial during the past 3 months. Participants who are willing to give written, signed and dated informed and consent to participate in the study were included in study.

Exclusion criteria

Patient who had prior ligament tear surgery of knee and shoulder joint in the past 6 months, torn or avulsed patellar or quadriceps tendon, periarticular or long bone fracture that is anticipated to preclude weight-bearing after surgery, patients who are unable to bear weight on the contralateral uninjured leg, traumatic brain injury (TBI) that limits their ability to participate in their post-operative care, surgical procedures that precludes early weight-bearing or range of motion, any condition that would preclude the ability to comply with post-operative guidelines. Moderate to severe renal impairment, pregnant or lactating women, history of hypersensitivity to any of the test products and any systemic condition of patient decided as unfit for study by clinical investigator were excluded.

Investigational drug

Ligashot-one tablet twice daily orally after food for 12 weeks. Ligashot tablet composition is shown in Table 1.

Duration of study drug given was 12 weeks.

Primary outcome

Changes from baseline to 12 weeks in pain intensity measured by pain VAS (0-100 mm). Time to return to pre-injury level of activity. Patient-reported physical function-activity limitation scale of the multiple ligament QoL (MLQoL) questionnaire.

The activity limitation scale score ranges from 0 to 100 with a score of 0 representing no activity limitations due to knee, shoulder ligament injury.

Changes from base line to 3 months in following laboratory parameter(s): Hs-C reactive protein, ESR and improvement in MRI was also noted.

Global rating of change (GRC) [Time frame: 3 months]-The GRC asks the individual to compare his/her current functional status to his/her functional status at the time of enrolment/post-injury. The responses for the GRC range from +7 (greatly better) to-7 (greatly worse). Higher scores representing greater improvement in function since the time of enrolment.

Changes from base line to 3 months in QoL-questionnaires (Short form health-12).

Secondary outcome of the stud

Adverse drug reactions observed during the study period (for safety assessment).

Statistical analysis

Changes in score of pain intensity, improvement scores between baseline and at 4^th, 8^th and at 12^th week of treatment in Ligashot tablet is measured by repeated measures of ANOVA. Statistical significance is measured by p<0.05.

RESULTS

Age and gender wise distribution of patients with ligament injury of knee, shoulder in the study is depicted in Table 2.

Change from baseline to 12 weeks in joint pain intensity measured by pain VAS.

*There was a statistically significant improvement in the VAS pain score at week 4, week 8, and week 12 compared to baseline post-treatment with Ligashot.

At 8 weeks of treatment with Ligashot tablet, 40% of patients showed pre injury level of activity as shown in Table 4.

There was a significant improvement in the activity limitation score from pre to post study in tablet Ligashot group as shown in Table 5.

There was a statistically significant reduction in the primary inflammatory markers like ESR and Hs-CRP from baseline to week 12 after treatment with Ligashot as shown in Table 6.

Also, there was a statistically significant improvement in the participant's GRC at week 4, week 8, and week 12 (Mean±SD=4.80±1.89), p<0.0001 compared to baseline post-treatment with Ligashot.

The improvements observed in the MRI of the patients after study period of 12 weeks has been highlighted in Figure 1 (A and B).

Near complete tear of anterior cruciate ligament (ACL) and moderate joint effusion were found in pre study findings in MRI. Partial tears in ACL and minimal joint effusion found in post study findings after 3 months of treatment with tablet Ligashot as shown in Figure 1 A.

Grade II partial tear of ACL in the mid third region, low grade partial tears in the upper 1/3^rd of posterior cruciate ligament, degenerative changes in both medial and lateral menisci, an oblique tear in the posterior horn of medial meniscus seen in pre study MRI findings. While in post study MRI after treatment period, grade I partial tear of ACL in the mid third region, few old tiny tears noted in the upper 1/3^rd of the posterior cruciate ligament.

Partial tear of subscapularis in shoulder joint and mild joint effusion seen in pre study findings while in post study MRI after treatment period, no joint effusion seen.

The side effects observed were mostly gastrointestinal (nausea in 3 patients and gastritis in 4 patients) in the study group and no serious adverse effects were recorded during the study period.

*P<0.05. There was a significant improvement in the mean percentage scores of QoL-questionnaires on physical activity status after treatment for 12 weeks with Ligashot tablet.

DISCUSSION

Ligaments connect one bone to another and regulate the joint's range of motion. Ligament injury of knee and Shoulder results in abnormal knee kinematics and damage to surrounding tissues in and around the joint, leading to morbidity and pain.⁹ The rupture of the ACL, the sprain of the medial or lateral collateral ligament of the knee most commonly occurs in ligament injury of the knee.¹⁰ Ligashot Tablet is a nutraceutical, acting on the musculo-skeletal system of the body.

Vitamin C plays a crucial role in connective tissue healing, serving as a cofactor for the enzyme’s prolyl hydroxylase and lysyl hydroxylase. These enzymes catalyse the hydroxylation of proline and lysine residues in procollagen, facilitating the correct folding of the stable collagen triple-helix structure and help in ligament strenghthening.¹¹Aflapin obtained from Boswellia serrata gum resin exhibits superior anti-inflammatory, cartilage-protective property. An in vitro study indicated that aflapin has a protective effect against the chondrocyte-destructive properties of the proinflammatory cytokine IL-1β.¹²

In vivo study by Silva et al in rats, they found that combined glucosamine and chondroitin sulfate provides functional and structural benefit in the ACL transection model.¹³ Coury et al in their in vivo study showed that administration of curcumin lowered tissue and serum levels of pro-inflammatory cytokines and matrix Metallo proteinases (MMP) in ACL transection injury-induced model in rabbits.¹⁴ In a Ostojic et al randomized, double-blind study of glucosamine or a placebo for 28 days, the patients from the glucosamine group demonstrated significant improvement in pain intensity and functional capacity in knee injury.¹⁵

Each ingredient in Ligashot tablet help support bone health, reduce inflammation and pain, has antioxidant properties that can help in improving symptoms of ligament injury. In this study all ingredients together in a tablet form are evaluated for its efficacy in patients with grade 1 and 2 ligament injury of knee and shoulder. Our study showed a statistically significant reduction in inflammatory markers ESR and Hs-CRP (p<0.001) after 12 weeks of treatment with tablet Ligashot. There was also a statistically significant improvement after 12 weeks of treatment compared to baseline in VAS pain scale, MRI changes (Post study), time to return to pre-injury level of activity, patient reported physical function (p<0.0001) and in QoL questionnaire.

Limitations

This study was done without any comparator groups which may increase bias in outcome of study. Small sample size of study group in this study.

CONCLUSION

The test product tablet Ligashot has proved to be safe and effective in treating symptoms of Ligament injury of Knee, shoulder joint by reducing inflammation, pain and enhancing the visco-elasticity. It also improves the Participant's functional capacity without causing any major side effects.

Funding: Funding sources by Innovcare Lifesciences Pvt ltd, Mumbai)

Conflict of interest: None declared

Ethical approval: The study was approved by the Institutional Ethics Committee

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