Double-blind trial of the efficacy of pentoxifylline vs thalidomide for the treatment of type II reaction in leprosy. An open trial with clofazimine in the management of recurrent lepra reaction using thalidomide as a control drug. A randomized, double-blind, double-dummy, controlled dose comparison of thalidomide for treatment of erythema nodosum leprosum. Pulsed corticosteroid therapy in patients with chronic recurrent ENL: a pilot study. Comparison of the effectiveness of placebo, clomiphene citrate, mesterolone, pentoxifylline, and testosterone rebound therapy for the treatment of idiopathic oligospermia. A double-blind placebo-controlled study of clomipramine in depressed patients with Alzheimer's disease. A multicenter, investigator-blinded, randomized comparison of oral levofloxacin and oral clarithromycin in the treatment of acute bacterial sinusitis. Treatment of sudden sensorineural hearing loss with systemic steroids and valacyclovir. Double-blind controlled clinical trial of clofazimine in reactive phases of lepromatous leprosy. Controlled trial of antimycobacterial therapy in Crohn's disease. Clofazimine versus placebo. A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer's disease. A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. Treatment of recurrent aphthous stomatitis with clofazimine.
Type II reaction in leprosy, or erythema nodosum leprosum (ENL), is often characterized by severe clinical symptoms together with nerve function impairment leading to permanent disabilities. Thalidomide has been shown to be a highly effective drug for the treatment of ENL. It is, however, contraindicated for women of childbearing age due to its teratogenicity. On the other hand, pentoxifylline, used to treat hypercoagulable states, is not teratogenic and, like thalidomide, can inhibit the synthesis of tumor necrosis factor-a and other cytokines. In the present randomized double-blind clinical study we compared the effectiveness of orally administered pentoxifylline vs thalidomide in treating type II reaction in 44 patients. Daily doses of 300 mg thalidomide or 1.2 g pentoxifylline were administered for 30 days to multibacillary leprosy patients undergoing type II reaction. Randomly chosen patients were included in the study before, during, and after specific multidrug therapy. Clinical evaluations were performed on the 1st, 7th, 14th, 21st, and 30th days of treatment and laboratory tests were carried out on the 1st and 30th days. As expected, overall, thalidomide proved to be more effective in the treatment of type II leprosy reaction. Nevertheless, continuous treatment with pentoxifylline was effective in relieving the clinical signs of ENL, especially limb edema and systemic symptoms, in 62.5% of the patients. nan In a randomized, double-blind, double-dummy controlled study, 22 men with erythema nodosum leprosum (ENL) received six capsules containing either 100 mg (group A, n = 12) or 300 mg (group B, n = 10) of thalidomide daily for one week. A six-week, four capsules per day taper followed, in which group A received 50 mg/day of thalidomide in weeks 2 and 3, then dummy capsules in weeks 4 through 7, while group B had gradual decrements every two weeks. Both regimens caused comparable improvement in 19 patients at day 7 (group A [12 of 12] versus group B [7 of 10]; P = 0.08), but slower tapering in group B showed less re-emergence of ENL through week 7 (P = 0.02, versus group A). Most patients developed new lesions soon after stopping treatment. Slower tapering from a higher initial thalidomide dose may improve clinical ENL responses, but high recurrence rates after discontinuation indicates further assessment is needed to identify better tapering regimens. A pilot study has been undertaken to compare the efficacy of small dose pulsed betamethasone therapy with need based oral steroids in chronic recurrent erythema nodosum leprosum (ENL) patients. Though this mode of therapy was well tolerated, no advantage with intermittent steroid administration was observed. This could have been on account of small dose of steroid given monthly. Treatment of chronic recurrent erythema nodosum leprosum (ENL) patients continues to be unsatisfactory, particularly, because of nonavailability of thalidomide. Though corticosteroids are effective in suppressing all the manifestations and even restoring partially or fully the functional impairment, their side effects and dependence are equally troublesome. Based on (a) the reported efficacy and safety of intermittent use of corticosteroids in several immune complex mediated disorders (Cathcart et al 1976, Kimberly et al 1979), Liebling et al 1981 and Pasricha & Gupta 1984) and (b) ENL (type II) reactions having similar pathology, a pilot study has been undertaken to see the efficacy and the tolerance of pulsed steroids in chronic ENL patients. Forty-six subfertile men with idiopathic oligospermia were randomly assigned to 6 months of treatment with a placebo, clomiphene citrate (25 or 50 mg/day), mesterolone (100 mg/day), or pentoxifylline (1200 mg/day) or 4 months of testosterone enanthate treatment (100 or 250 mg on alternate weeks). Treatment with the placebo, mesterolone, pentoxifylline, and testosterone rebound therapy did not result in a significant increase in the mean sperm concentration or pregnancy in the partners. Clomiphene citrate at both dosages significantly increased the mean sperm concentration without improving sperm motility or morphology during the 6-month treatment period. Pregnancy rates of 36.4% and 22.2% were observed in partners of men receiving clomiphene citrate 25 mg/day and 50 mg/day, respectively. This study also illustrates the difficulties in identifying suitable patients for and assessing the efficacy of different treatment regimens. Twenty-one depressed patients with probable Alzheimer's disease (AD) were randomized to receive a 6-week treatment with clomipramine or placebo in a study with a double-blind crossover design. Main outcome measures were Hamilton Depression, Mini-Mental State (MMSE), and Functional Independence Measure (FIM) scores. Mood improved significantly on both clomipramine and placebo, but clomipramine was significantly more effective than placebo during the first 6-week treatment period. Patients started on clomipramine maintained improvement during the washout and placebo periods, whereas patients started on placebo worsened during the washout period. However, patients on clomipramine showed significantly lower MMSE scores overall than patients on placebo. No significant drug effects were found on FIM scores. Clomipramine proved to be a useful treatment of depression in patients with probable AD. A multicenter, investigator-blinded, randomized, parallel-group study was conducted to compare oral levofloxacin 500 mg once/day for 14 days with clarithromycin 500 mg twice/day for 14 days in the treatment of acute bacterial sinusitis. Of 216 adult outpatients randomized to treatment, 190 were evaluable for efficacy. The primary efficacy measure was clinical response, based on resolution of signs and symptoms 2-5 days after therapy. A secondary efficacy measure was relapse rate 1 month after therapy. Among evaluable patients, clinical success rates (cured or improved) were 96.0% and 93.3% for levofloxacin (L) and clarithromycin (C), respectively (95% CI -9.2%, 3.7%). The confidence interval (CI) for treatment difference (C-L) included zero and its upper limit was less than 15%, indicating that levofloxacin was as effective as clarithromycin. In all, 4.1% of patients receiving levofloxacin and 7.2% receiving clarithromycin had a relapse of symptoms 1 month after therapy (95% CI-12.2%, 3.2%). Long-term success (initial success, absence of relapse at 1 month, no further antibacterial therapy 2-5 days after therapy) was 79.2% in the levofloxacin group and 76.4% in the clarithromycin group (95% CI -14.7%, 9.0%). Based on investigator-assessed treatment-emergent adverse events, overall tolerability of the drugs was similar, except for a higher frequency of taste perversion and diarrhea in the clarithromycin group. Levofloxacin had an advantage over clarithromycin based on two quality-of-life (QOL) parameters: number of times taking other drugs for targeted medical conditions and mean total cost of these drugs. No statistical significance was found in other QOL variables. These findings suggest that the efficacy and tolerability of levofloxacin 500 mg once/day are comparable with those of clarithromycin 500 mg twice/day in the treatment of acute bacterial sinusitis. To determine if the addition of an antiviral medication to systemic steroids improves recovery in the treatment of idiopathic sudden sensorineural hearing loss.
                Randomized, double-blind, placebo-controlled prospective multicenter clinical trial.
                The study was administrated from a tertiary care center and clinical research institute; patients were enrolled by otolaryngologists in academic and private practice outpatient settings.
                Inclusion criteria included 1) loss of at least 30 dB in 3 contiguous frequencies over <3 days in patients with previous audiometry, 2) marked loss of hearing in patients with prior subjectively normal hearing and no previous audiometry, with contralateral hearing taken as baseline, and 3) patients seen within 10 days of onset of hearing loss. Pretreatment evaluation included audiometry and complete blood cell count, complete blood chemistry, and fluorescent treponemal antibody absorption test. Auditory brainstem-evoked response or magnetic resonance imaging was recommended.
                Patients received prednisone (80 mg/d for 4 d, then tapered over 8 d) with placebo or prednisone with valacyclovir (1 g, 3 times a day for 10 days).
                1) Audiometric assessment at presentation, Week 2, and Week 6; 2) Hearing Screening Inventory questionnaire twice weekly for 6 weeks; and 3) acute Short Form-12 questionnaire at presentation and Week 2.
                Of 105 subjects enrolled in the study, 84 subjects were evaluable. There were no significant differences between placebo and valacyclovir treatment groups in terms of hearing recovery or symptom recovery on the basis of the Hearing Screening Inventory or Short Form-12 questionnaires. No adverse events were related to the use of valacyclovir.
                Within the paradigm used in the current study, an antiviral medication did not provide more benefit than steroid alone in the treatment of idiopathic sudden sensorineural hearing loss. A double-blind controlled trial in 24 lepromatous leprosy patients in reaction showed that clofazimine (Lamprene) controlled symptoms of erythema nodosum leprosum reaction in lepromatous leprosy better than prednisolone. Clofazimine also appeared to be significantly superior in preventing recurrence once the reaction had been controlled. There was a statistically significant rise in serum albumin among inpatients on clofazimine as compared with patients on prednisolone, but no difference in terms of neurological status, bacterial index, morphological index, and renal functions. Red/black hyperpigmentation was seen among practically all patients on clofazimine. No other side-effects or deleterious systemic effects were observed. In order to study the effect of clofazimine, a powerful antimycobacterial and antiinflammatory agent, 49 patients with active Crohn's disease were randomized to either corticosteroids plus clofazimine 100 mg daily (N = 25) or to steroids and matching placebo (N = 24). A total of 28 patients (58%) went into disease remission (clofazimine 16, placebo 12; P = NS) with a fall in disease activity score from 10.5 +/- 4.4 to 3.3 +/- 3.5. Patients were treated for a further eight months with clofazimine or placebo and 18 of 28 maintained their remission and completed the study (clofazimine 12, placebo 6; P = NS). Side effects were minor and consisted of skin rash and increased pigmentation. Clofazimine as a solitary antimycobacterial agent appears ineffective in inducing remission in Crohn's disease but may have a role in either disease maintenance or combination chemotherapy. Previous studies suggest a potential benefit from nonsteroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease (AD). Prescribing NSAIDs, however, carries the risk of significant gastrointestinal adverse events.
                To study whether treatment with an NSAID prevents expected decline in AD patients and evaluate whether co-administration of the gastro-protective agent, misoprostol, with an NSAID is safe in AD.
                The efficacy and safety of diclofenac in combination with misoprostol (D/M) was evaluated in 41 patients with mild-moderate AD in a prospective 25-week, randomized, double-blind placebo-controlled trial. Efficacy measures comprised the Alzheimer's Disease Assessment Scale cognitive and noncognitive subsections, Global Deterioration Scale, Clinical Global Impression of Change, Mini-Mental State Examination, Instrumental Activities of Daily Living, Physical Self-Maintenance Scale, and a caregiver-rated Global Impression of Change.
                There were no group differences with any of the outcome measures in an intent-to-treat analysis. There were some nonsignificant trends for the placebo group to have deteriorated more than the D/M-treated patients. Withdrawal rates were 12 of 24 in the D/M group and 2 of 17 in the placebo group. There were no serious drug-related adverse events.
                This pilot study, with small treatment numbers, did not demonstrate a significant effect of NSAID treatment in AD, but the trends observed justify further investigations with a larger number of participants. D/M is safe in AD patients, but its tolerability is not optimal. To determine whether clomipramine hydrochloride, a serotonin reuptake blocker with unique anti-obsessional properties, is differentially effective for obsessive-compulsive and stereotyped motor behaviors in autistic disorder compared with placebo and with the noradrenergic tricyclic antidepressant agent, desipramine hydrochloride.
                Following a 2-week, single-blind placebo washout phase, 12 autistic subjects completed a 10-week, double-blind, crossover comparison of clomipramine and placebo, and 12 different subjects completed a similar comparison of clomipramine and desipramine.
                Outpatient clinic.
                A referral sample of 30 male and female autistic patients were enrolled, and 24 completed the study.
                Key outcome measures were the Autism Relevant Subscale of the Children's Psychiatric Rating Scale, the Modified Comprehensive Psychopathological Rating Scale-Obsessive-Compulsive Disorder Subscale, and the Clinical Global Impressions Scale.
                Clomipramine was superior to both placebo and desipramine on ratings of autistic symptoms (including stereotypies), anger, and compulsive, ritualized behaviors (P < .05), with no differences between desipramine and placebo. Clomipramine was equal to desipramine and both tricyclic agents were superior to placebo for amelioration of hyperactivity.
                Biological links between compulsions and stereotyped, repetitive behaviors in autistic disorder should be explored. The aim was to investigate the safety and efficacy of clofazimine for the treatment of recurrent aphthous stomatitis.
                In this randomized controlled partially blind study, 23 patients received clofazimine 100 mg daily for 30 days and then 100 mg every other day. Twenty-three patients received colchicine 0.5 mg 3 times daily. Twenty patients received 1 placebo pill 2 times daily. All subjects received medications for 6 months. The chi-squared or Fisher exact tests were used to assess drug efficacy with respect to objective findings and symptoms.
                A greater percentage of individuals in the clofazimine group had no further aphthous episodes (17%-44% compared with <or=6% in the other groups). A significantly greater percentage of treatment interruption occurred in the colchicine group because of gastrointestinal effects (23%-45%). Individuals in the clofazimine group who continued to suffer from aphthous stomatitis presented with better results for the evaluated variables.
                Clofazimine should be considered for the treatment of recurrent aphthous stomatitis.
There is some evidence of benefit for thalidomide and clofazimine, but generally we did not find clear evidence of benefit for interventions in the management of ENL. However, this does not mean they do not work, because the studies were small and poorly reported. Larger studies using clearly defined participants, outcome measures, and internationally recognised scales are urgently required.