Evaluation of efficacy and safety of Collashot C2 plus capsule in osteoarthritis patients

INTRODUCTION

Osteoarthritis (OA) is a joint disorder that leads to pain, stiffness, restricted movement and disability mostly in the elderly. The prevalence of OA in India is about 22-39% and is more common in women.¹ The disease typically affects the knee but can also impact the hips, hands, shoulders, and spine.² OA, particularly in the hip and knee, leads to significant locomotor disability.³ Medical management of OA includes weight reduction, physiotherapy, and pharmacotherapy (mainly non-steroidal anti-inflammatory drugs), which provide modest benefits, primarily aiming to reduce pain and improve joint mobility and quality of life.^4,5 Collashot C2 plus capsule is a nutraceutical, which contains Commiphora myrrha extract 4% (MyrLiq)-100 mg, choline -60 mg, Curcuma longa extract-50 mg, Boswellia serrata extract-50 mg, native (Undenatured) collagen type-II-40 mg, sodium hyaluronate-40 mg.

Commiphora myrrha extract contains phytochemicals like terpenoids, triterpenoids, and steroids which has anti-inflammatory activity.⁶ Choline-stabilized ortho-silicic acid promotes the activity of osteoblasts, their differentiation and the production of osteo-pontin, osteocalcin, alkaline phosphatase.⁷ Curcumin longa extract-pharmacological use is by its ability to inhibit nuclear factor-Kappa B (NF-κB) pathway and by acting as a scavenger of reactive oxygen and nitrogen species.⁸ Boswellia serrata also known as Salai guggul, has potent anti-inflammatory effect that can effectively relieve pain and help prevent cartilage loss.⁹ Type II collagen has positive effects on inflammation and in degradative joint diseases.

It is a nutritional supplement indicated for joint pain, swelling, stiffness and other symptoms of arthritis. The capsule increases bone strength and mineral content and reduces the chance of falls and fractures.¹⁰ Many drugs are available in the market for treating Osteo arthritis symptoms but there is still need for drugs with least adverse effects. So, in this study, an attempt has been done with Collashot C2 plus capsule for treating OA symptoms.

METHODS

The present study is an outcome, quasi-experimental study where patients with OA according to inclusion criteria were included and assessed after treatment. Patients were given capsule Collashot C2 plus daily for 3 months. Collashot C2 plus capsule sponsored by Innovcare lifesciences pvt ltd, Mumbai. The study was done in Thirumalai medical centre and in Sri ortho care clinic in Pondicherry during September 2023-April 2024.The study was registered in clinical trial registry of India CTRI/2023/09/057515. Independent ethics committee approval obtained for this study from Ethique De La nature association in 19^th August 2023.

Inclusion criteria

Participants with OA of knee joint based on American college of rheumatology (ACR) criteria and confirmed with X-rays and ACR functional class of III and with grade 3 or 4 as per Kellgren and Lawrence classification system. Participants who were on stable doses of nonsteroidal anti-inflammatory drugs (NSAIDS) of at least 2000 mg per day for at least 20 days in the past month. Participants with OA pain defined by a level greater than or equal to 30 mm on a 100 mm VAS. The participant who had not participated in any other clinical trial during the past 3 months. Participants, who were willing to give written, signed, and dated informed consent to participate in the study were included in study.

Exclusion criteria

Arthritis of knee from other systemic causes, uncontrolled hypertension or diabetes, patients having OA pain that requires treatment with potent opioids, systemic corticosteroids, intra-articular injections, duloxetine or venlafaxine, moderate to severe renal impairment, pregnant or lactating women, patients who received any other investigational medicine within 7 days prior to screening which can interfere with investigational product activity, participants who suffered from any illness which will interfere with the present study as decided by the clinical investigator and history of hypersensitivity to any of the test product composition were excluded.

Investigational drug

Collashot C2 plus-One capsule daily orally after food in the morning for 12 weeks. Collashot capsule composition is shown in Table 1.

*Choline-stabilized orthosilicic acid.

Duration of study drug given was 12 weeks.

Primary outcome

Change from baseline to 12 weeks in knee pain intensity measured by pain VAS scale (0-100 nm). Change from baseline to 12 weeks in the WOMAC pain subscale. [Maximum score=96 (Worst condition), minimum score=0 (Best condition)]. Changes from baseline to 12 weeks in the following laboratory parameter(s): Hs-C reactive Protein (high sensitivity C-reactive protein), ESR and C-telopeptide. Change in baseline to 12 weeks in participant's global assessment of improvement of OA. (0-to-10-point scale: 0-less disease activity and 10-more disease activity). Number of participants with a response rate measured by the outcome measures for rheumatology committee and OA research society international standing committee for clinical trials response criteria initiative (OMERACT-OARSI). Changes from baseline to 12 weeks in quality of life-questionnaires (Short form health-12).

Secondary outcome

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 Collashot capsule group is measured by repeated measures of ANOVA. Statistical significance is measured by p<0.05.

RESULTS

Age and gender wise distribution of patients with Osteoarthritis included in the study is depicted in Table 2.

Knee pain intensity by pain VAS scale was assessed between baseline and 4^th, 8^th and 12 weeks of treatment in Collashot C2 plus group OA patients shown in Table 3.

*Statistically significant.

Maximum score=96 (Worst condition), minimum score=0 (Best condition).

There was a statistically significant improvement in the WOMAC pain score at week 4, week 8, and week 12 compared to the baseline after treatment with the Collashot C2 plus.

Reduction in ESR and Hs CRP levels when compared to baseline and after 12 weeks treatment showed in the Figure 1.

*There was a statistically significant improvement (reduction) in the C telopeptide levels which is a marker of bone resorption/degeneration, from baseline to week 12 after treatment with Collashot C2 plus.

*0-to-10-point scale: 0-Less disease activity and 10-more disease activity.

There was a statistically significant improvement in the participant's global assessment score at week 4, week 8, and week 12 compared to baseline post-treatment with Collashot C2 plus as shown in Table 6.

There was a good response percentage of improvement after treatment with Collashot C 2 plus shown in Table 7, as evidenced by the response rate measured by the OMERACT-OARSI beginning from week 4 week to week 12.

Changes from baseline in quality of life-questionnaires (Short form health-12) from baseline to 12 weeks of study drug shown in Table 8.

*There was a significant improvement in the mean percentage scores of quality of life-questionnaires on physical activity status after treatment for week 12 with Collashot C2 plus p<0.05.

Adverse effects during the study period shown in Table 9.

DISCUSSION

OA, the most prevalent joint disease, is marked by chronic joint pain and debilitating symptoms. OA, particularly in the hip and knee, leads to significant locomotor disability. Collashot C2 plus capsule is a nutraceutical, which contains Commiphora myrrha extract 4% (MyrLiq)-100 mg, choline -60 mg, Curcuma longa extract-50 mg, Boswellia serrata extract-50 mg, native undenatured collagen type II-40 mg, sodium hyaluronate-40 mg. It is a nutraceutical indicated for joint pain, swelling, stiffness and other symptoms of arthritis.

Commiphora myrrha extract, also known as myrrh, is a resin that comes from the bark of Commiphora myrrha plant. It has analgesic, anti-inflammatory and antioxidant properties.¹¹ Choline-stabilized orthosilicic acid is a bioavailable and stable form of silicon. Supplementation promotes the mineralization of the bone matrix.¹²

Curcumin longa has immense pharmacological properties like anti-inflammatory, antioxidant and also has anticancer activity.¹³ Hsiao et al in a meta-analysis with Curcumin longa extract with a total of 1258 participants in 11 randomised trials in patients with knee OA, showed more pain relief than non-steroidal anti-inflammatory drugs.¹⁴

The resinous component of Boswellia serrata contains monoterpenes, diterpenes, triterpenes, tetracyclic triterpenic acids and four major pentacyclic triterpenic acids. It has potent anti-inflammatory that can effectively relieve pain and help prevent cartilage loss.¹⁵ Collagen type-II is the main structural component of the cartilage tissue. It is a nutraceutical derived from chicken sternum cartilage. In Bakilan et al study native undenatured type II collagen with acetaminophen is more effective than using acetaminophen alone for alleviating symptoms in patients with knee OA.¹⁶ Cicero et al in a study found that Oral supplementation with sodium hyaluronate has been linked to short-term improvement in symptoms and functionality in patients with OA.¹⁷

Each ingredient in Collashot C2 plus capsule has shown anti-inflammatory activity and improvement in patients with OA in clinical trials. In this study all ingredients together in a capsule is evaluated for its efficacy in osteo arthritis patients. Our study also showed a statistically significant improvement in the VAS pain scale, WOMAC pain score, significant reduction in inflammatory parameters (ESR, C-telopeptide, Hs-CRP levels) and improvement in participant's global assessment of OA at week 4, week 8, and week 12 compared to baseline (p<0.001).

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 Collashot C2 plus has proved to be very safe and effective in the management of OA participants by reducing inflammation, providing adequate pain relief and by improving the participant's functional capacity without causing any major side effects.

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

Conflict of interest: Yes - study drug sponsored by Innovcare Lifesciences Pvt Ltd, Mumbai

Ethical approval: The study was approved by the Institutional Ethics Committee, CTRI/2023/09/057515.

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