Effects of laterally wedged insoles on symptoms and disease progression in medial knee osteoarthritis: a protocol for a randomised,double-blind,placebo controlled trial

Background  

Whilst laterally wedged insoles, worn inside the shoes, are advocated as a simple, inexpensive, non-toxic self-administered intervention for knee osteoarthritis (OA), there is currently limited evidence to support their use. The aim of this randomised, double-blind controlled trial is to determine whether laterally wedges insoles lead to greater improvements in knee pain, physical function and health-related quality of life, and slower structural disease progression as well as being more cost-effective, than control flat insoles in people with medial knee OA.     

Terodiline, emepronium bromide or placebo for treatment of female detrusor overactivity? A randomised, double-blind, cross-over study

In a randomised, double-blind study, 20 women with idiopathic detrusor instability and associated symptoms were treated with terodiline 25 mg bd, placebo, and emepronium bromide 200 mg tds--each drug being given for 3 weeks with placebo as wash-out period before cross-over. The results were evaluated according to drug preference, frequency charts and elimination of detrusor instability on cystometry. Serum levels of both drugs were monitored as control of tablet intake. The preference for terodiline to placebo was statistically significant: 14/3 women (P less than 0.05), and the majority of women (12/4) preferred terodiline to emepronium. Terodiline also gave a small but significant reduction in 24 h micturition frequency and eliminated detrusor instability in almost 50% of the patients (P less than 0.05). Side effects were frequent but mild in all three treatment periods. It was concluded that terodiline offers an alternative in the treatment of female detrusor instability.     

A double-blind trial of suloctidil v. placebo in intermittent claudication

In a recent double-blind trial lasting over 6 months, 40 patients suffering from intermittent claudication were randomly allocated to receive 300 mg of suloctidil per day or exactly matching placebo capsules. In addition to treadmill walking distance, other objective criteria including ankle blood pressure response and muscle blood flow measured by 133Xe clearance were used to assess the effectiveness of therapy. Nine patients (4 in the suloctidil group and 5 controls) did not complete the trial according to the protocol. Of the remaining 31 patients, 17 were in the control group and 14 received suloctidil. A significant improvement in the absolute walking distance, the level of beta-thromboglobulin (beta TG) compared to pre-therapy value and the time for the ankle pressure index to return to the pre-exercise value was observed in patients receiving suloctidil.     

Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo

Serotonin (5-HT) plays a crucial role in mediating the descending pain inhibitory systems and in the pathophysiology of migraine. Previous studies regarding the use of 5-Hydroxytryptophan (5-HTP), the active precursor of 5-HT, in the treatment of Chronic Primary Headache (CPH) have been inconclusive so far. In order to assess the efficacy of the serotonin active precursor in chronic headache prophylaxis, a double-blind cross-over study has been carried out in 31 patients with CPH, comparing L-5-HTP to placebo. Clinical syndromes included: (a) migraine (16 patients); (b) mixed headache (6 patients); (c) psychogenic headache (5 patients); (d) muscle contraction headache (4 patients). L-5-HTP was administered for two months at daily doses of 400 mg p.o. The reduction in severity and frequency of headache in patients taking the active drug and placebo was noted. Mood patterns were also taken into consideration. L-5-HTP proved to be more effective than placebo in reducing both headache frequency and severity, but the difference was not statistically significant. Favourable responses (greater than 50% average reduction in headache symptoms) were obtained in 48% of the cases after the second month of treatment. No significant difference in therapeutic response was observed as related to different clinical syndromes, except for psychogenic headache patients, who responded poorly to the active drug. Side effects, experienced in 19% of the cases, were generally mild and transient. We conclude that L-5-HTP is a medication of moderate efficacy and remarkable safety, providing us with another alternative approach to CPH prophylaxis.     

A double-blind cross-over trial of trimethoprim and sulphamethoxazole in chronic bronchitis

A double-blind cross-over trial comparing trimethoprim-sulphamethoxazole with sulphamethoxazole in patients with chronic bronchitis in their usual state of health showed that the combination was more effective in reducing the volume and purulence of the sputum. Although the patients preferred treatment with the combination, there was no objective improvement in respiratory function. There was a significant incidence of side effects.     

Homotoxicological remedies versus desmopressin versus placebo in the treatment of enuresis: a randomised, double-blind, controlled trial

The aim of this trial was to compare the safety and efficacy of homotoxicological remedies versus placebo and versus desmopressin (dDAVP) in the treatment of monosymptomatic nocturnal enuresis (MNE). We conducted a randomised, double-blind, double-dummy, controlled trial in which 151 children with MNE were randomly assigned to receive oral homotoxicological remedies (n = 50), dDAVP (n = 50) or placebo (n = 51). The primary outcomes were: the reduction of wet nights per week after 3 months of therapy; the evaluation of the numbers and percentages of non-responders and responders; the number of children relapsing after initial response and the number of children attaining 14 consecutive dry nights during the treatment. The secondary outcome was the detection of adverse effects. Baseline clinical characteristics were similar in the three groups of patients. After the 3 months of therapy there was a significant difference between the three groups (P < 0.001) in the mean number of wet nights per week. The daily dose of dDAVP produced a statistically significant decrease (62.9%) in wet nights compared to placebo (2.4%) (P < 0.001) and compared to homotoxicological remedies (30.0%) (P < 0.001). There was a significant decrease in wet nights among the group treated with homotoxicological medications if compared with placebo (P < 0.001). The full response achieved with homotoxicological remedies (20%) was superior if compared with placebo (0%) (P < 0.001). Homotoxicology was superior to placebo (P < 0.001) with regard to the number of children attaining 14 consecutive dry nights during treatment. Our study demonstrates that homotoxicology is safe and effective when compared with placebo, even if it is significantly less effective than dDAVP in this clinical condition.     

Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo

OBJECTIVE: To investigate the efficacy and tolerability of a 3-month duration, twice a-year, intermittent treatment with oral chondroitin sulfate (CS) in knee osteoarthritis (OA) patients. DESIGN: A total of 120 patients with symptomatic knee OA were randomized into two groups receiving either 800mg CS or placebo (PBO) per day for two periods of 3 months during 1 year. Primary efficacy outcome was Lequesne's algo-functional index (AFI); secondary outcome parameters included VAS, walking time, global judgment, and paracetamol consumption. Radiological progression was assessed by automatic measurement of medial femoro-tibial joint space width on weight-bearing X-rays of both knees. Clinical and biological tolerability was assessed. RESULTS: One hundred and ten of 120 patients were included in the ITT analysis. AFI decreased significantly by 36% in the CS group after 1 year as compared to 23% in the PBO group. Similar results were found for the secondary outcomes parameters. Radiological progression at month 12 showed significantly decreased joint space width in the PBO group with no change in the CS group. Tolerability was good with only minor adverse events identically observed in both groups. CONCLUSION: This study provides evidences that oral CS decreased pain and improved knee function. The 3-month intermittent administration of 800mg/day of oral CS twice a year does support the prolonged effect known with symptom-modifying agents for OA. The inhibitory effect of CS on the radiological progression of the medial femoro-tibial joint space narrowing could suggest further evidence of its structure-modifying properties in knee OA.     

A randomised controlled trial of micronised purified flavonoid fraction vs placebo in patients with chronic venous disease.

OBJECTIVE: to evaluate the efficacy of a micronised purified flavonoid fraction (MPFF) in the treatment of chronic venous disease (CVD). DESIGN: prospective double blind, randomised, control study. PATIENTS and METHODS: one hundred and one patients with symptomatic CVD were randomly allocated to treatment for 60 days with either MPFF (51 patients) or placebo (50 patients) 500 mg twice daily. There were 28 men and 73 women, aged 22-65 years (mean age 48 years). No difference regarding age, gender, clinical class or duration of symptoms was recorded between the treatment and placebo groups. A global score for evaluation of symptoms was used. Patients were investigated with plethysmography (foot-volumetry) and duplex-ultrasonography before and after the treatment period. For statistical comparison Cochran-Mantel-Haenszel test, two-sided Student t-test and covariance analysis were used and p<0.05 was regarded significant. RESULTS: improvement of the global score of symptoms was reported by 21 patients in the MPFF group and by 16 in the placebo group (N.S.). For the whole groups, no significant differences were recorded before and after treatment regarding foot-volumetric or ultrasonographic parameters. On the other hand, in patients with edema (20 in the MPFF group, 23 in the placebo group) ultrasonographic reflux time was significantly reduced for those in the treatment group (p=0.03). This finding did not correlate to clinical symptoms. CONCLUSION: in this study, MPFF did not change the symptoms of CVD, except night cramps. A secondary finding was reduced reflux times in patients with oedema, although no ultrasonographic or foot-volumetric parameters changed significantly for the whole group. The role of MPFF in treatment of patients with CVD needs to be further analysed in a large population.     

A randomised controlled trial of tidal irrigation vs corticosteroid injection in knee osteoarthritis: the KIVIS Study

OBJECTIVES: Patients with knee osteoarthritis (OA) often suffer pain that is not fully controlled by analgesics and often require intra-articular therapies. The aim of this study was to compare the benefits of intra-articular corticosteroid injections (CSIs) and tidal irrigation (TI) in patients with OA of the knee. METHODS: We performed a dual-centre, single blind, randomised, parallel group trial comparing TI and CSI. Patients with knee OA were randomised to either irrigation using a 3.2mm arthroscope under local anaesthesia or an intra-articular injection of 40 mg triamcinolone acetonide and 1% lidocaine. Patients were followed for 6 months. The primary outcome measure was the Western Ontario and McMaster Universities OA Index total pain score (visual analogue scale, VAS). RESULTS: One hundred and fifty patients were recruited of whom 71 received TI and 79 CSI. In both treatment groups, over 80% of patients reported improvement at 2 and 4 weeks. After this time, the benefit of CSI decreased whereas that of TI was maintained: at 26 weeks the pain relief afforded by TI was significantly greater than that of CSI. At 26 weeks 29% of the CSI group reported improvement vs 64% of the TI group (P<0.001). Patients with a knee effusion responded better to both treatments, however, this was most apparent for CSI. Patients with less severe radiographic OA also obtained the greatest improvement from both treatments. CONCLUSION: Both procedures lead to significant short-term pain relief of at least 4 weeks, however, TI displayed a significantly greater duration of benefit. Patients with effusions and milder radiographic change obtained the best response to treatment.     

S-Adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial. [ISRCTN36233495]

Background  

S-Adenosylmethionine (SAMe) is a dietary supplement used in the management of osteoarthritis (OA) symptoms. Studies evaluating SAMe in the management of OA have been limited to Non Steroidal Anti-inflammatory Drugs (NSAIDs) for comparison. The present study compares the effectiveness of SAMe to a cyclooxygenase-2 (COX-2) inhibitor (celecoxib) for pain control, functional improvement and to decrease side effects in people with osteoarthritis of the knee.     

Harpagophytum procumbens in the treatment of knee and hip osteoarthritis. Four-month results of a prospective, multicenter, double-blind trial versus diacerhein

OBJECTIVE: To evaluate the efficacy and safety of Harpagophytum in the treatment of hip and knee osteoarthritis comparatively with the slow-acting drug for osteoarthritis, diacerhein. PATIENTS AND METHODS: A multicenter, randomized, double-blind, parallel-group study was conducted in 122 patients with hip and/or knee osteoarthritis. Treatment duration was four months and the primary evaluation criterion was the pain score on a visual analog scale. Harpagophytum 2,610 mg per day was compared with diacerhein 100 mg per day. RESULTS: After four months, considerable improvements in osteoarthritis symptoms were seen in both groups, with no significant differences for pain, functional disability, or the Lequesne score. However, use of analgesic (acetaminophen-caffeine) and nonsteroidal anti-inflammatory (diclofenac) medications was significantly reduced in the Harpagophytum group, which also had a significantly lower rate of adverse events. CONCLUSION: In this study, Harpagophytum was at least as effective as a reference drug (diacerhein) in the treatment of knee or hip osteoarthritis and reduced the need for analgesic and nonsteroidal anti-inflammatory therapy.