human
***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 Cancer-induced muscle wasting begins early in the course of a patient 's malignant disease , result ing in declining physical function and other detrimental clinical consequences . This r and omised , double-blind , placebo-controlled phase 2 trial assessed the efficacy and safety of enobosarm , a selective and rogen receptor modulator , in patients with cancer . METHODS We enrolled male ( > 45 years ) and female ( postmenopausal ) patients with cancer who were not obese and who had at least 2 % weight loss in the previous 6 months . Participants were r and omly assigned ( 1:1:1 ratio , by computer generated list , block size three , stratified by cancer type ) to receive once-daily oral enobosarm 1 mg , 3 mg , or placebo for up to 113 days at US and Argentinian oncology clinics . The sponsor , study personnel , and participants were masked to assignment . The primary endpoint was change in total lean body mass from baseline , assessed by dual-energy x-ray absorptiometry . Efficacy analyses were done only in patients who had a baseline and an on-treatment assessment in the protocol -specified window of within 10 days before baseline or first study drug , and within 10 days of day 113 or end of study ( evaluable efficacy population ) . Adverse events and other safety measurements were assessed in the intention-to-treat ( safety ) population . This trial is registered with Clinical Trials.gov , number NCT00467844 . FINDINGS Enrolment started on July 3 , 2007 , and the last patient completed the trial on Aug 1 , 2008 . 159 patients were analysed for safety ( placebo , n=52 ; enobosarm 1 mg , n=53 ; enobosarm 3 mg , n=54 ) . The evaluable efficacy population included 100 participants ( placebo , n=34 ; enobosarm 1 mg , n=32 ; enobosarm 3 mg , n=34 ) . Compared with baseline , significant increases in total lean body mass by day 113 or end of study were noted in both enobosarm groups ( enobosarm 1 mg median 1·5 kg , range -2·1 to 12·6 , p=0·0012 ; enodosarm 3 mg 1·0 kg , -4·8 to 11·5 , p=0·046 ) . Change in total lean body mass within the placebo group ( median 0·02 kg , range -5·8 to 6·7 ) was not significant ( p=0·88 ) . The most common serious adverse events were malignant neoplasm progression ( eight of 52 [ 15 % ] with placebo vs five of 53 [ 9 % ] with enobosarm 1 mg vs seven of 54 [ 13 % ] with enobosarm 3 mg ) , pneumonia ( two [ 4 % ] vs two [ 4 % ] vs three [ 6 % ] ) , and febrile neutropenia ( three [ 6%vs one [ 2 % ] vs none ) . None of these events were deemed related to study drug . INTERPRETATION Cancer cachexia is an unmet medical need and our data suggest that use of enobosarm might lead to improvements in lean body mass , without the toxic effects associated with and rogens and progestational agents . FUNDING GTx BACKGROUND Age-related losses of muscle mass , strength , and function ( sarcopenia ) pose significant threats to physical performance , independence , and quality of life . Nutritional supplementation could positively influence aspects of sarcopenia and thereby prevent mobility disability . OBJECTIVE To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of sarcopenia . DESIGN A multicenter , r and omized , controlled , double-blind , 2 parallel-group trial among 380 sarcopenic primarily independent-living older adults with Short Physical Performance Battery ( SPPB ; 0 - 12 ) scores between 4 and 9 , and a low skeletal muscle mass index . The active group ( n = 184 ) received a vitamin D and leucine-enriched whey protein nutritional supplement to consume twice daily for 13 weeks . The control group ( n = 196 ) received an iso-caloric control product to consume twice daily for 13 weeks . Primary outcomes of h and grip strength and SPPB score , and secondary outcomes of chair-st and test , gait speed , balance score , and appendicular muscle mass ( by DXA ) were measured at baseline , week 7 , and week 13 of the intervention . RESULTS H and grip strength and SPPB improved in both groups without significant between-group differences . The active group improved more in the chair-st and test compared with the control group , between-group effect ( 95 % confidence interval ) : -1.01 seconds ( -1.77 to -0.19 ) , P = .018 . The active group gained more appendicular muscle mass than the control group , between-group effect : 0.17 kg ( 0.004 - 0.338 ) , P = .045 . CONCLUSIONS This 13-week intervention of a vitamin D and leucine-enriched whey protein oral nutritional supplement result ed in improvements in muscle mass and lower-extremity function among sarcopenic older adults . This study shows proof-of-principle that specific nutritional supplementation alone might benefit geriatric patients , especially relevant for those who are unable to exercise . These results warrant further investigations into the role of a specific nutritional supplement as part of a multimodal approach to prevent adverse outcomes among older adults at risk for disability OBJECTIVES To investigate the effects of exercise and /or nutritional supplementation on body composition , blood components , and physical function in community-dwelling elderly Japanese women with sarcopenic obesity . DESIGN R and omized controlled trial . SETTING Urban community in Tokyo , Japan . PARTICIPANTS Among 1213 community-dwelling elderly women over 70 years of age , 307 were defined with sarcopenic obesity , and 139 women participated in the study . INTERVENTION Participants were r and omly assigned to one of four intervention groups . The exercise and nutrition ( Ex + N ) and exercise only ( Ex ) groups attended 60-minute exercise classes twice a week for 3 months . The Ex + N and nutrition only ( N ) groups were provided with essential amino acid supplementation and tea fortified with catechins to be taken daily for 3 months . Health education classes were provided to the control ( HE ) group every 2 weeks . MEASUREMENTS Bioelectric impedance analysis was used to measure body composition . Skeletal muscle mass index was calculated using measures of muscle mass and height . Physical function measures included grip strength , knee extension strength , usual walking speed , and walking parameters ( stride , step length , width , walking angles ) . Blood sample s were obtained to analyze levels of albumin , triglycerides , cholesterol , hemoglobin A1c , leptin , cystatin C , vitamin D , interleukin-6 , and high-sensitivity C-reactive protein . RESULTS Significant between-group × time interactions were observed in usual walking speed ( P = .012 ) , stride ( P = .004 ) , right step length ( P = .003 ) , average number of steps ( P = .029 ) , and vitamin D ( P < .001 ) . Compared to the HE group , the Ex + N intervention significantly decreased total body fat mass ( P = .036 ) and increased stride ( P = .038 ) and vitamin D ( P < .001 ) . Significant reductions in trunk fat were observed in the Ex group compared with HE ( P = .014 ) . The Ex + N and Ex interventions were over four times as likely ( odds ratio [ 95 % confidence interval ] ) to reduce body fat mass than the HE group ( 4.42 [ 1.21 - 16.19 ] ; 4.50 [ 1.13 - 17.9 ] , respectively ) . Significant odds ratios of the Ex + N intervention improving walking speed ( 3.05 [ 1.01 - 9.19 ] ) , vitamin D ( 14.22 [ 1.64 - 123.02 ] ) , and leptin ( 3.86 [ 1.19 - 12.47 ] ) were also observed . CONCLUSION Although exercise and nutrition have beneficial effects on individual variables of body composition , blood components , and physical function , improvements in muscle mass and variable combinations such as percent fat + skeletal muscle mass index or percent fat + physical functions were not observed in this population . Further large-scale and long-term investigation is necessary Objective : To study activin signaling and its blockade in sporadic inclusion body myositis ( sIBM ) through translational studies and a r and omized controlled trial . Methods : We measured transforming growth factor β signaling by SMAD2/3 phosphorylation in muscle biopsies of 50 patients with neuromuscular disease ( 17 with sIBM ) . We tested inhibition of activin receptors IIA and IIB ( ActRII ) in 14 patients with sIBM using one dose of bimagrumab ( n = 11 ) or placebo ( n = 3 ) . The primary outcome was the change in right thigh muscle volume by MRI at 8 weeks . Lean body mass , strength , and function were secondary outcomes . Twelve of the patients ( 10 bimagrumab , 2  placebo )  participated in a subsequent 16-week observation phase . Results : Muscle SMAD2/3 phosphorylation was higher in sIBM than in other muscle diseases studied ( p = 0.003 ) . Eight weeks after dosing , the bimagrumab-treated patients increased thigh muscle volume ( right leg + 6.5 % compared with placebo , p = 0.024 ; left leg + 7.6 % , p = 0.009 ) and lean body mass ( + 5.7 % compared with placebo , p = 0.014 ) . Subsequently , bimagrumab-treated patients had improved 6-minute walking distance , which peaked at 16 weeks ( + 14.6 % , p = 0.008 ) compared with placebo . There were no serious adverse events ; the main adverse events with bimagrumab were mild acne and transient involuntary muscle contractions . Conclusions : Transforming growth factor β superfamily signaling , at least through ActRII , is implicated in the pathophysiology of sIBM . Inhibition of ActRII increased muscle mass and function in this pilot trial , offering a potential novel treatment of sIBM . Classification of evidence : This study provides Class I evidence that for patients with inclusion body myositis  , bimagrumab increases thigh muscle volume at 8 weeks Protein supplementation in combination with resistance training may increase muscle mass and muscle strength in elderly subjects . The objective of this study was to assess the influence of post-exercise protein supplementation with collagen peptides v. placebo on muscle mass and muscle function following resistance training in elderly subjects with sarcopenia . A total of fifty-three male subjects ( 72·2 ( sd 4·68 ) years ) with sarcopenia ( class I or II ) completed this r and omised double-blind placebo-controlled study . All the participants underwent a 12-week guided resistance training programme ( three sessions per week ) and were supplemented with either collagen peptides ( treatment group ( TG ) ) ( 15 g/d ) or silica as placebo ( placebo group ( PG ) ) . Fat-free mass ( FFM ) , fat mass ( FM ) and bone mass ( BM ) were measured before and after the intervention using dual-energy X-ray absorptiometry . Isokinetic quadriceps strength ( IQS ) of the right leg was determined and sensory motor control ( SMC ) was investigated by a st and ardised one-leg stabilisation test . Following the training programme , all the subjects showed significantly higher ( P<0·01 ) levels for FFM , BM , IQS and SMC with significantly lower ( P<0·01 ) levels for FM . The effect was significantly more pronounced in subjects receiving collagen peptides : FFM ( TG + 4·2 ( sd 2·31 ) kg/PG + 2·9 ( sd 1·84 ) kg ; P<0·05 ) ; IQS ( TG + 16·5 ( sd 12·9 ) Nm/PG + 7·3 ( sd 13·2 ) Nm ; P<0·05 ) ; and FM ( TG –5·4 ( sd 3·17 ) kg/PG –3·5 ( sd 2·16 ) kg ; P<0·05 ) . Our data demonstrate that compared with placebo , collagen peptide supplementation in combination with resistance training further improved body composition by increasing FFM , muscle strength and the loss in FM BACKGROUND Cancer anorexia-cachexia syndrome is associated with increased morbidity and mortality . Anamorelin is an oral ghrelin-receptor agonist with appetite-enhancing and anabolic activity . We assessed the effects of anamorelin on body composition , strength , quality of life , biochemical markers , and safety in patients with cancer anorexia-cachexia . METHODS Data were pooled , a priori , from two completed phase 2 , multicentre , placebo-controlled , double-blind trials in patients with advanced or incurable cancer and weight loss of 5 % or more . Patients were stratified by weight loss severity ( 5 - 15 % , > 15 % ) and r and omly allocated ( 1:1 ) with a computer-generated r and omisation schedule to anamorelin hydrochloride 50 mg or placebo once-daily for 12 weeks . 
    Output:
    
agent
There is a lack of robust evidence to assess the strength of other treatment options
***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 Cancer-induced muscle wasting begins early in the course of a patient 's malignant disease , result ing in declining physical function and other detrimental clinical consequences . This r and omised , double-blind , placebo-controlled phase 2 trial assessed the efficacy and safety of enobosarm , a selective and rogen receptor modulator , in patients with cancer . METHODS We enrolled male ( > 45 years ) and female ( postmenopausal ) patients with cancer who were not obese and who had at least 2 % weight loss in the previous 6 months . Participants were r and omly assigned ( 1:1:1 ratio , by computer generated list , block size three , stratified by cancer type ) to receive once-daily oral enobosarm 1 mg , 3 mg , or placebo for up to 113 days at US and Argentinian oncology clinics . The sponsor , study personnel , and participants were masked to assignment . The primary endpoint was change in total lean body mass from baseline , assessed by dual-energy x-ray absorptiometry . Efficacy analyses were done only in patients who had a baseline and an on-treatment assessment in the protocol -specified window of within 10 days before baseline or first study drug , and within 10 days of day 113 or end of study ( evaluable efficacy population ) . Adverse events and other safety measurements were assessed in the intention-to-treat ( safety ) population . This trial is registered with Clinical Trials.gov , number NCT00467844 . FINDINGS Enrolment started on July 3 , 2007 , and the last patient completed the trial on Aug 1 , 2008 . 159 patients were analysed for safety ( placebo , n=52 ; enobosarm 1 mg , n=53 ; enobosarm 3 mg , n=54 ) . The evaluable efficacy population included 100 participants ( placebo , n=34 ; enobosarm 1 mg , n=32 ; enobosarm 3 mg , n=34 ) . Compared with baseline , significant increases in total lean body mass by day 113 or end of study were noted in both enobosarm groups ( enobosarm 1 mg median 1·5 kg , range -2·1 to 12·6 , p=0·0012 ; enodosarm 3 mg 1·0 kg , -4·8 to 11·5 , p=0·046 ) . Change in total lean body mass within the placebo group ( median 0·02 kg , range -5·8 to 6·7 ) was not significant ( p=0·88 ) . The most common serious adverse events were malignant neoplasm progression ( eight of 52 [ 15 % ] with placebo vs five of 53 [ 9 % ] with enobosarm 1 mg vs seven of 54 [ 13 % ] with enobosarm 3 mg ) , pneumonia ( two [ 4 % ] vs two [ 4 % ] vs three [ 6 % ] ) , and febrile neutropenia ( three [ 6%vs one [ 2 % ] vs none ) . None of these events were deemed related to study drug . INTERPRETATION Cancer cachexia is an unmet medical need and our data suggest that use of enobosarm might lead to improvements in lean body mass , without the toxic effects associated with and rogens and progestational agents . FUNDING GTx BACKGROUND Age-related losses of muscle mass , strength , and function ( sarcopenia ) pose significant threats to physical performance , independence , and quality of life . Nutritional supplementation could positively influence aspects of sarcopenia and thereby prevent mobility disability . OBJECTIVE To test the hypothesis that a specific oral nutritional supplement can result in improvements in measures of sarcopenia . DESIGN A multicenter , r and omized , controlled , double-blind , 2 parallel-group trial among 380 sarcopenic primarily independent-living older adults with Short Physical Performance Battery ( SPPB ; 0 - 12 ) scores between 4 and 9 , and a low skeletal muscle mass index . The active group ( n = 184 ) received a vitamin D and leucine-enriched whey protein nutritional supplement to consume twice daily for 13 weeks . The control group ( n = 196 ) received an iso-caloric control product to consume twice daily for 13 weeks . Primary outcomes of h and grip strength and SPPB score , and secondary outcomes of chair-st and test , gait speed , balance score , and appendicular muscle mass ( by DXA ) were measured at baseline , week 7 , and week 13 of the intervention . RESULTS H and grip strength and SPPB improved in both groups without significant between-group differences . The active group improved more in the chair-st and test compared with the control group , between-group effect ( 95 % confidence interval ) : -1.01 seconds ( -1.77 to -0.19 ) , P = .018 . The active group gained more appendicular muscle mass than the control group , between-group effect : 0.17 kg ( 0.004 - 0.338 ) , P = .045 . CONCLUSIONS This 13-week intervention of a vitamin D and leucine-enriched whey protein oral nutritional supplement result ed in improvements in muscle mass and lower-extremity function among sarcopenic older adults . This study shows proof-of-principle that specific nutritional supplementation alone might benefit geriatric patients , especially relevant for those who are unable to exercise . These results warrant further investigations into the role of a specific nutritional supplement as part of a multimodal approach to prevent adverse outcomes among older adults at risk for disability OBJECTIVES To investigate the effects of exercise and /or nutritional supplementation on body composition , blood components , and physical function in community-dwelling elderly Japanese women with sarcopenic obesity . DESIGN R and omized controlled trial . SETTING Urban community in Tokyo , Japan . PARTICIPANTS Among 1213 community-dwelling elderly women over 70 years of age , 307 were defined with sarcopenic obesity , and 139 women participated in the study . INTERVENTION Participants were r and omly assigned to one of four intervention groups . The exercise and nutrition ( Ex + N ) and exercise only ( Ex ) groups attended 60-minute exercise classes twice a week for 3 months . The Ex + N and nutrition only ( N ) groups were provided with essential amino acid supplementation and tea fortified with catechins to be taken daily for 3 months . Health education classes were provided to the control ( HE ) group every 2 weeks . MEASUREMENTS Bioelectric impedance analysis was used to measure body composition . Skeletal muscle mass index was calculated using measures of muscle mass and height . Physical function measures included grip strength , knee extension strength , usual walking speed , and walking parameters ( stride , step length , width , walking angles ) . Blood sample s were obtained to analyze levels of albumin , triglycerides , cholesterol , hemoglobin A1c , leptin , cystatin C , vitamin D , interleukin-6 , and high-sensitivity C-reactive protein . RESULTS Significant between-group × time interactions were observed in usual walking speed ( P = .012 ) , stride ( P = .004 ) , right step length ( P = .003 ) , average number of steps ( P = .029 ) , and vitamin D ( P < .001 ) . Compared to the HE group , the Ex + N intervention significantly decreased total body fat mass ( P = .036 ) and increased stride ( P = .038 ) and vitamin D ( P < .001 ) . Significant reductions in trunk fat were observed in the Ex group compared with HE ( P = .014 ) . The Ex + N and Ex interventions were over four times as likely ( odds ratio [ 95 % confidence interval ] ) to reduce body fat mass than the HE group ( 4.42 [ 1.21 - 16.19 ] ; 4.50 [ 1.13 - 17.9 ] , respectively ) . Significant odds ratios of the Ex + N intervention improving walking speed ( 3.05 [ 1.01 - 9.19 ] ) , vitamin D ( 14.22 [ 1.64 - 123.02 ] ) , and leptin ( 3.86 [ 1.19 - 12.47 ] ) were also observed . CONCLUSION Although exercise and nutrition have beneficial effects on individual variables of body composition , blood components , and physical function , improvements in muscle mass and variable combinations such as percent fat + skeletal muscle mass index or percent fat + physical functions were not observed in this population . Further large-scale and long-term investigation is necessary Objective : To study activin signaling and its blockade in sporadic inclusion body myositis ( sIBM ) through translational studies and a r and omized controlled trial . Methods : We measured transforming growth factor β signaling by SMAD2/3 phosphorylation in muscle biopsies of 50 patients with neuromuscular disease ( 17 with sIBM ) . We tested inhibition of activin receptors IIA and IIB ( ActRII ) in 14 patients with sIBM using one dose of bimagrumab ( n = 11 ) or placebo ( n = 3 ) . The primary outcome was the change in right thigh muscle volume by MRI at 8 weeks . Lean body mass , strength , and function were secondary outcomes . Twelve of the patients ( 10 bimagrumab , 2  placebo )  participated in a subsequent 16-week observation phase . Results : Muscle SMAD2/3 phosphorylation was higher in sIBM than in other muscle diseases studied ( p = 0.003 ) . Eight weeks after dosing , the bimagrumab-treated patients increased thigh muscle volume ( right leg + 6.5 % compared with placebo , p = 0.024 ; left leg + 7.6 % , p = 0.009 ) and lean body mass ( + 5.7 % compared with placebo , p = 0.014 ) . Subsequently , bimagrumab-treated patients had improved 6-minute walking distance , which peaked at 16 weeks ( + 14.6 % , p = 0.008 ) compared with placebo . There were no serious adverse events ; the main adverse events with bimagrumab were mild acne and transient involuntary muscle contractions . Conclusions : Transforming growth factor β superfamily signaling , at least through ActRII , is implicated in the pathophysiology of sIBM . Inhibition of ActRII increased muscle mass and function in this pilot trial , offering a potential novel treatment of sIBM . Classification of evidence : This study provides Class I evidence that for patients with inclusion body myositis  , bimagrumab increases thigh muscle volume at 8 weeks Protein supplementation in combination with resistance training may increase muscle mass and muscle strength in elderly subjects . The objective of this study was to assess the influence of post-exercise protein supplementation with collagen peptides v. placebo on muscle mass and muscle function following resistance training in elderly subjects with sarcopenia . A total of fifty-three male subjects ( 72·2 ( sd 4·68 ) years ) with sarcopenia ( class I or II ) completed this r and omised double-blind placebo-controlled study . All the participants underwent a 12-week guided resistance training programme ( three sessions per week ) and were supplemented with either collagen peptides ( treatment group ( TG ) ) ( 15 g/d ) or silica as placebo ( placebo group ( PG ) ) . Fat-free mass ( FFM ) , fat mass ( FM ) and bone mass ( BM ) were measured before and after the intervention using dual-energy X-ray absorptiometry . Isokinetic quadriceps strength ( IQS ) of the right leg was determined and sensory motor control ( SMC ) was investigated by a st and ardised one-leg stabilisation test . Following the training programme , all the subjects showed significantly higher ( P<0·01 ) levels for FFM , BM , IQS and SMC with significantly lower ( P<0·01 ) levels for FM . The effect was significantly more pronounced in subjects receiving collagen peptides : FFM ( TG + 4·2 ( sd 2·31 ) kg/PG + 2·9 ( sd 1·84 ) kg ; P<0·05 ) ; IQS ( TG + 16·5 ( sd 12·9 ) Nm/PG + 7·3 ( sd 13·2 ) Nm ; P<0·05 ) ; and FM ( TG –5·4 ( sd 3·17 ) kg/PG –3·5 ( sd 2·16 ) kg ; P<0·05 ) . Our data demonstrate that compared with placebo , collagen peptide supplementation in combination with resistance training further improved body composition by increasing FFM , muscle strength and the loss in FM BACKGROUND Cancer anorexia-cachexia syndrome is associated with increased morbidity and mortality . Anamorelin is an oral ghrelin-receptor agonist with appetite-enhancing and anabolic activity . We assessed the effects of anamorelin on body composition , strength , quality of life , biochemical markers , and safety in patients with cancer anorexia-cachexia . METHODS Data were pooled , a priori , from two completed phase 2 , multicentre , placebo-controlled , double-blind trials in patients with advanced or incurable cancer and weight loss of 5 % or more . Patients were stratified by weight loss severity ( 5 - 15 % , > 15 % ) and r and omly allocated ( 1:1 ) with a computer-generated r and omisation schedule to anamorelin hydrochloride 50 mg or placebo once-daily for 12 weeks . 
    Output:
    