Intra-articular infiltrative therapy associated with alpha lipoic acid and vegetable saffron extract vs intra-articular infiltrative therapy only, in moderate-to-severe arthrosic pain - Pathos

All the variables detected in the data collection form are shown in descriptive tables. In particular, the continuous variables are presented as averages, SD, median, minimum and maximum, while the moderate and nominal variables are shown in contingency tables with the frequencies and the respective percentages. When appropriate, the homogeneity of the variables with respect to the two treatment groups was assessed by the Chi-square test (qualitative variables) or the ANOVA test (quantitative variables).

1. The level of analgesia according to the NRS scale (pain intensity at rest and load and/or movement)

2. Physical well-being

3. Functionality of joints

4. Quality of sleep

5. Joint mobility

The comparison of the results obtained in the course of treatment will be evaluated using the numerical assessment scale at 11 points (0-10 NRS) and the ADL scale assessing autonomy in daily living activities.

The normality of data distribution will be evaluated by Kolmogorov-Smirnov tests.

The comparison of the temporal trend of the variables will be performed via the ANOVA test for repeated measurements (normal variables) or non-parametric tests for abnormal variables (e.g. Friedman).

• Patients diagnosed with arthritis of the shoulder, knee or hip;

• With the presence of average daily pain ≥4 measured with NRS and reported in last 24 hours, attributable to the arthritic pathology;

• Able to comply with the study treatment;

• Aged 18 or over;

• Who have signed the informed consent.

• Participation in other research projects that are in conflict or that could confuse the results of the study;

• Absence of informed consent, or withdrawal of consent, for participation in the study;

• Presence of concomitant psychiatric pathological conditions that could interfere with the state of consciousness or with the ability to judge;

• Contraindications of any kind to the use of the treatment in question;

• For reasons connected to the study treatment (adverse event);

• For reasons not connected to treatment (death due to illness, transfer of the patient to another treatment facility);

• For reasons connected to the patient (withdrawal of consent, poor compliance);

• For various reasons (protocol violations, administrative problems);

The study requires the reporting of release from follow-up, the date, and the related reasons.

The patient included in the study protocol must be monitored and evaluated in the manner and times described in the protocol.   

The information necessary for this purpose is contained in the patient data sheet drawn up at the time of enrolment and consist of:

• Patient personal data (age, sex);

• Study inclusion and exclusion criteria based on the checklist;

• Patient information and obtaining of informed consent in reference to participation in the study;

• Assignment of treatment.

• Summary medical history, which includes the indication on the arthritic pathology, the date of its first diagnosis, the secondary localizations present at that time, and the previously performed treatments;  

• Possible concomitant diseases in progress;  

• All treatments (analgesic and non-analgesic) in place before visit 1;  

• Adverse reactions due to antalgic treatments prior to the start of the study;

• Performance status in daily living activities expressed with the ADL scale;

• Information related to the patient’s pain: how many months the patient suffers from pain due to arthritis of the shoulder, knee or hip, the intensity of the average and worst pain experienced in the last 24 hours (with NRS, on patient's indication), the characteristics and type of pain (nociceptive), neuropathic, mixed).  

• Measure the amount of average and worst pain related to the last 24 hours (with NRS, on patient's indication);

• Reporting of recourse to additional therapy to support the treatment with the study drugs under starting from the previous visit;

• Addition of fixed, variable pain therapy plan (additional therapy and rescue) and other therapies decided upon to visit;

• Reporting of any change in the study drug and its causes;

• Performance status expressed with the ADL scale;

• Upon indication of the patient, any adverse reactions correlated with pain therapy and any other adverse events;

• Report of any early termination of the study and its related causes.

The main population for efficacy evaluation is the Intent-to-treat population (ITT) composed of all eligible, randomised patients, with the evaluation of the primary efficacy variable at baseline and at least one post-baseline detection. One Per-protocol population" also evaluated, to support the ITT population composed of patients who have concluded the study regularly, without protocol violations, and who have taken the same type of treatment for the duration of the study.  

For the evaluation of tolerability, we take into consideration the "Safety population" consisting of patients who have been given at least one dose of the study treatment assigned to them.

In spontaneous pain/rest conditions, both groups showed significant improvement over the 2 months of treatment (P<0.001) (Figure 1). A repeated two-way variance analysis (interaction in the treatment time) was used. The two groups as the factor between the subjects (treatment) and the six measurements at the time point during the treatment were considered as internal factors (time).

The comparison between tretments was not statitically significant at any visit.

As shown in Figure 1, the group of patients treated with intra-articular infiltrative therapy associated with oral alpha lipoic acid and saffron vegetable extract Tabs 1100 mg / day (group 1) therapy, during the 60-day observation span had a of the NRS scale score equal to 2.92% on average. The group of patients treated with intra-articular infiltrative therapy alone (group 2) had a reduction of the NRS scale score equal to 2.54% on average over the 60-day observation period.

Under load/movement pain conditions both groups showed significant improvement over the 2-month treatment (P<0.001). Group 1 significantly reduced the NRS average value compared to the control indicated by the factor effect between subjects (P<0.001).

A repeated two-way variance analysis (interaction of time in the treatment) was used. The two groups as the factor between the subjects (treatment) and the six measurements at the time point during the treatment were considered as internal factors (time). If time-dependent changes were significant at each stage, the Dunnett test was used as a post-hoc test to compare the decrease in pain intensity with baseline values. If the treatment-dependent changes were significant, t-tests were used to compare the differences between the two treatments for each time point. P values ​​of ≤0.05 were considered to indicate statistical significance. The data is given as means ± SEM.

At the baseline visit for both treatment groups, almost all patients reported reduced or poor physical well-being. The start of treatment shows a progressive and constant improvement of the conditions of the patients, in particular group 1. The percentage of patients in group 1 with improved physical well-being increased from 33.3 percent in the first week of observation, to 90 percent in the second week and remained so until the 30th day, and then reached 96% at the 45 days of observation. At the end of the period, however, there was a trend reversal with the percentage reduced to 73.3.  For group 2 patients who were only treated with infiltrative therapy, no improvement in physical well-being was recorded after the first week of observation. In the second week, 60 percent showed an improvement, at 30 days the percentage rose to 80 percent. Later, there was a downturn of the trend at 45 days, which was reduced to 40 percent, and then to only 26.6 percent at the end of the observation period (Figure 3).

The primary objective proposed in the study was to evaluate the pain related to osteoarthritis of the shoulder, knee or hip, using a numerical 11-point evaluation scale (0-10 NRS) and the autonomy in daily living rating scale (ADL). The secondary objectives concerned the benefits in terms of mobility, physical well-being, joint functionality and sleep quality. The intensity of spontaneous/resting pain shows a decreasing temporal course for both treatment groups and although the group treated with alpha lipoic acid and saffron vegetable extract 1100 mg tablets (group 1) showed a greater improvement, the statistical analysis did not show a significant difference between the values ​​found in all the follow-up intervals. On the other hand, the analysis of the values ​​selected in the load/movement pain condition, namely when the pain is decidedly greater, was more significant.