***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Adjuvant endocrine therapy can improve disease-free survival and time before recurrence in breast cancer patients . However , it is associated with considerable side effects that negatively affect patients ’ quality of life and cause non-adherence . The recently demonstrated effect of individual expectations on side-effect development ( nocebo effect ) suggests that psychological factors play a role in the prevention of side effects . The aim of this study is to evaluate cognitive-behavioral side-effect prevention training ( SEPT ) for breast cancer patients . This article describes the study protocol and applied research methods . Methods / Design In a r and omized controlled trial , 184 female breast cancer patients are assigned to receive either SEPT , st and ard medical care or a manualized supportive therapy at the start of adjuvant endocrine treatment . SEPT consists of three sessions of cognitive-behavioral training including psychoeducation to provide a realistic view of endocrine therapy , imagination-training to integrate positive aspects of medication into daily life , and side-effect management to enhance expectations about coping ability . Side effects three months after the start of endocrine therapy serve as primary outcomes . Secondary outcomes include quality of life , coping ability and patients ’ medication adherence . Patients ’ expectations ( i.e. , expectations about side effects , coping ability , treatment and illness ) are analyzed as mediators . Discussion The optimization of expectations might be a potential pathway in health care to improve patients ’ quality of life during long-term medication intake . The results will provide implication s for a possible integration of evidence -based prevention training into clinical practice .Trial registration Clinical Trials.gov , ( NCT01741883 ) We initiated a double-blind , placebo-controlled trial to test the efficacy and safety of branched-chain amino acids ( BCAA ) ( L-leucine 12 g , L-isoleucine 6 g , and L-valine 6 g daily ) in amyotrophic lateral sclerosis ( ALS ) patients . There was an excess mortality in subjects r and omized to active treatment ( 24 BCAA , 13 placebo ) when a total of 126 ALS patients had been recruited . This finding , associated with the lack of efficacy of BCAA ( measured by comparing the disability scales in the two treatment groups ) , led the Data Monitoring Committee to require cessation of the trial BACKGROUND Amyotrophic lateral sclerosis ( ALS ) is a progressive disease with no effective treatment . In an initial study , riluzole decreased mortality and slowed muscle-strength deterioration in ALS patients . We have carried out a double-blind , placebo-controlled , multicentre study to confirm those findings and to assess drug efficacy at different doses . METHODS 959 patients with clinical ly probable or definite ALS of less than 5 years ' duration were r and omly assigned treatment with placebo or 50 mg , 100 mg , or 200 mg riluzole daily ; r and omisation was stratified by centre and site of disease onset ( bulbar or limb ) . The primary outcome was survival without a tracheostomy . Secondary outcomes were rates of change in functional measures ( muscle strength , functional status , respiratory function , patient 's assessment s of fasciculation , cramps , stiffness , and tiredness ) . The primary analysis was the comparison of the 100 mg dose with placebo by intention-to-treat . Drug-effect on survival was assessed before ( log-rank test ) and after adjustment for known prognostic factors ( Cox 's model ) . FINDINGS At the end of the study , after median follow-up of 18 months , 122 ( 50.4 % ) placebo-treated patients and 134 ( 56.8 % ) of those who received 100 mg/day riluzole were alive without tracheostomy ( unadjusted risk 0.79 , p = 0.076 ; adjusted risk 0.65 , p = 0.002 ) . In the groups receiving 50 mg and 200 mg riluzole daily , 131 ( 55.3 % ) and 141 ( 57.8 % ) patients were alive without tracheostomy ( relative to placebo 50 mg adjusted risk 0.76 , p = 0.04 ; 200 mg 0.61 , p = 0.0004 ) . There was a significant inverse dose response in risk of death . No functional scale discriminated between the treatment groups . The most common adverse reactions were asthenia , dizziness , gastrointestinal disorders , and rises in liver enzyme activities ; they were commonest with the 200 mg dose . INTERPRETATION Overall , efficacy and safety results suggest that the 100 mg dose of riluzole has the best benefit-to-risk ratio . This study confirms that riluzole is well tolerated and lengthens survival of patients with ALS BACKGROUND The cause of amyotrophic lateral sclerosis ( ALS ) is not known , and there is no effective treatment . Cell death may be caused by oxidative damage . Selegiline hydrochloride ( Eldepryl ) is a monoamine oxidase-B inhibitor with antioxidant properties . OBJECTIVE To determine if selegiline affects the clinical course of patients with ALS . DESIGN Six-month , double-blind , placebo-controlled study of 133 patients with classical ALS and symptoms for less than 3 years . The primary end point to indicate effectiveness was the rate of change of the Appel ALS total score , an index of disease severity that incorporates strength and function in limbs , respiratory function , and bulbar function . RESULTS Of the 133 patients , 67 were r and omized to receive selegiline and 66 to receive placebo . One hundred four patients ( 53 in the selegiline group and 51 in the placebo group ) completed the 6-month trial . Both groups were comparable for baseline characteristics and mean Appel ALS total score ( 70.5 points for the selegiline group and 70.6 for the placebo group ) . There was no difference in the rate of progression as measured by the Appel ALS total score , showing an average increase of 22 points in 6 months . The monthly rate of change was 3.4 for the selegiline group and 3.5 for the placebo group . There was 1 adverse reaction : worsening depression . Seven patients died during the study ( 4 in the selegiline group and 3 in the placebo group ) . CONCLUSION Selegiline treatment had no significant effect on the rate of clinical progression or outcome of ALS Abstract Treatment with the neuroprotective drug riluzole has previously been shown to increase the probability of survival in patients with amyotrophic lateral sclerosis . This report describes a placebo-controlled , double-blind r and omised clinical trial of riluzole carried out in ALS patients with advanced stage disease or aged over 75 years . The primary objective was to enable access to treatment to patients excluded from the pivotal trial which was run in parallel . Another goal was to assess the safety of riluzole in patients with advanced-stage disease . One hundred and sixty-eight patients were included , r and omised to either riluzole 50 mg b. i. d. or to placebo , and treated for eighteen months . Riluzole was well-tolerated in this patient population , and the adverse events observed were similar in nature and frequency to those observed in previously published clinical trials in patients included in pivotal trials . The study could not include enough patients to reach adequate power to detect differences in survival between the two treatment groups , and no such difference was in fact observed . In conclusion , riluzole is well-tolerated in ALS patients with advanced stage disease Ciliary neurotrophic factor ( CNTF ) is a neuroactive cytokine found in Schwann cells , which appears to be released in response to nerve injury . The ALS CNTF Treatment Study ( ACTS ) clinical trial was a phase II-III r and omized , placebo-controlled , double-blind study design ed to evaluate the safety , tolerability , and efficacy of subcutaneous administration of recombinantly produced human CNTF ( rHCNTF ) in slowing disease progression in 730 patients with amyotrophic lateral sclerosis ( ALS ) . Patients were r and omized to receive 30 micrograms/kg or 15 micrograms/kg rHCNTF or placebo subcutaneously three times a week for 9 months . The primary endpoint of the study , the slope of decline of isometric muscle strength in treated versus placebo patients , showed no statistically significant difference between rHCNTF and placebo-treated patients , and was complicated by an initial statistically significant decrease in strength early in rHCNTF-treated patients . Mortality was similar in all three study arms . There were no statistically significant treatment effects among the secondary measures . Side effects of rHCNTF included anorexia , weight loss , and cough and were sufficient to limit dosing in many patients & NA ; Discovery of the involvement of endogenous opiates in placebo analgesia represents an important step in underst and ing the mechanisms underlying placebo response . In the present study , we investigated the effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia in a human model of experimentally induced ischemic pain . First , we found that part of the placebo response was reversed by naloxone , confirming previous studies on the role of opioids in the placebo phenomenon . Second , since it was demonstrated that the action of exogenous and endogenous opiates is potentiated by proglumide , we analysed the effects of this cholecystokinin antagonist on placebo response and found that it enhanced placebo analgesia . The placebo effect can thus be modulated in two opposite directions : it can be partially abolished by naloxone and potentiated by proglumide . The fact that placebo potentiation  by proglumide occurred only in placebo responders , but not in non‐responders , suggests that activation of an endogenous opiate system is a necessary condition for the action of proglumide . These results suggest an inhibitory role for cholecystokinin in placebo response , although the low affinity of proglumide for cholecystokinin receptors does not rule out the possibility of other mechanisms We design ed a phase II trial to evaluate the efficacy of gabapentin in slowing the rate of decline in muscle strength of patients with amyotrophic lateral sclerosis ( ALS ) and to assess safety and tolerability .  Gabapentin ( 800 mg ) or placebo was administered t.i.d . in a r and omized , double-blinded , placebo-controlled , trial for 6 months . We enrolled 152 patients at eight sites in the United States . The primary outcome measure was the slope of the arm megascore , the average maximum voluntary isometric strength from eight arm muscles st and ardized against a reference ALS population . A secondary outcome measure was forced vital capacity . Slopes of arm megascores for patients on gabapentin were compared with slopes of those taking placebo using a two-way ANOVA . We observed a nonstatistically significant trend ( p = 0.057 - 0.08 ) toward slower decline of arm strength in patients taking gabapentin compared with those taking placebo ( mean difference 24 % , median 37 % ) . We observed no treatment effect on forced vital capacity .  Gabapentin was well tolerated by patients with ALS . These results suggest that further studies of gabapentin in ALS are warranted Background : Pre clinical and clinical studies of gabapentin in patients with ALS led the authors to undertake a phase III r and omized clinical trial . Methods : Patients were r and omly assigned , in a double-blinded fashion , to receive oral gabapentin 3,600 mg or placebo daily for 9 months . The primary outcome measure was the average rate of decline in isometric arm muscle strength for those with two or more evaluations . Results : Two hundred four patients enrolled , 196 had two or more evaluations , and 128 patients completed the study . The mean rate of decline of the arm muscle strength was not significantly different between the groups . Moreover , there was no beneficial effect upon the rate of decline of other secondary measures ( vital capacity , survival , ALS functional rating scale , timed walking ) nor was there any symptomatic benefit . In fact , analysis of the combined data from the phase II and III trials revealed a significantly more rapid decline of forced vital capacity in patients treated with gabapentin . Conclusion : These data provide no evidence of a beneficial effect of gabapentin on disease progression or symptoms in patients with ALS Calcium channel blocking drugs antagonize excitatory amino acid receptor activation , decrease calcium entry into damaged neurons , and might help to slow or reverse amyotrophic lateral sclerosis ( ALS ) . We enrolled 87 patients with ALS in a r and omized , placebo-controlled  , prospect i ve , double-blind crossover study of  nimodipine therapy . Monthly measures of isometric muscle strength and respiratory function compared the effects of drug and placebo . No difference in adverse events occurred in placebo vs drug-treated patients , but diarrhoea , nausea , and lightheadedness were more common with nimodipine . There was no significant difference in the rate of decline of pulmonary function or limb strength during treatment with drug or placebo . Nimodipine was ineffective in slowing the progress of ALS BACKGROUND Amyotrophic lateral sclerosis is a progressive motor neuron disease for which there is no adequate treatment . Some research suggests that the excitatory amino acid neurotransmitter glutamate may be involved in the pathogenesis . METHODS To evaluate the efficacy and safety of the antiglutamate agent riluzole , we conducted a prospect i ve , double-blind , placebo-controlled trial in 155 out patients with amyotrophic lateral sclerosis . The dose of riluzole was 10 
    Output:
    
Our study indicates significant nocebo in trials for MND treatment , adversely affecting adherence and efficacy of current treatments in clinical practice , with additional implication s for trial design