TABLE 1.
Studies identified using multimodal interventions for cachexia1
| Intervention modality | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Reference | Disease | Participants | Study type | Length of study | Definition of wasting | Exercise | Diet/ONSs | Drugs | Control (n) | Key findings | QA |
| van Beers et al. (35) | COPD | 81 | RCT | 12 mo | FFMI below sex and age-specific 25th percentile. FFMI values defined by Schutz et al. (36) | Adjunct exercise: cycle ergometry and treadmill walking (40 training sessions supervised 2–3/wk; plus motivational counseling in maintenance phase >4 mo) | ONS (187 kcal/125 mL; 2–3×/d, with leucine, Ω-3 PUFAs, vitamin D) | X | Placebo exercise and noncaloric cloudified aqueous solution (n = 39) | Treatment group reported improvements in plasma concentrations2 and HADS.2 EQ-5D-3L decreased in placebo group only. Both groups increased physical capacity but treatment group exceeded the minimal important difference to reduce risk of hospital admission. Trend towards weight gain in treatment group and weight loss in placebo led to between-group difference at 12 mo.2 | 3 |
| Calder et al. (37) | COPD | 68 | RCT | 12 wk | Precachectic (PC) and cachectic according to European Respiratory Society UWL >5% (PC) or UWL >5% with FFMI of <17 kg/m2 (M) or 15 kg/m2 (F) | X | 200 mL/200 kcal 2×/d (10 g whey protein) and 10 μg vitamin D | 2 g Ω-3 PUFAs | 200 mL of milk-based comparator with no 25-hyroxyvitamin D2, milk protein instead of pure whey protein, and sunflower oil in place of Ω-3 PUFA–containing fish (n = 23) | BW increase in both groups but treatment group gained more fat mass.2 Reduced blood pressure,2 triglycerides,2 exercise-induced fatigue,2 and dyspnea,2 and increases in HDL cholesterol2 in treatment group. Compliance and safety profile similar in both groups. | 3 |
| van Wetering et al. (38) | COPD | 39 | RCT | 24 mo | Muscle wasting according to Vermeeren et al. (39), UWL at least 5% in 1 mo or ≥10% in 6 mo with BMI <25 kg/m2 | Exercise (cycling and walking and upper and lower strength and endurance training; home-based 30 min 2×/wk) | ONS 3× 125 mL (564 kcal) daily followed by 20 mo INS maintenance program | X | Individualized education program (n = 16) | Changes in favor of treatment group at 24 mo; maximum inspiration mouth pressure,2 quadriceps average power,2 6MWT,2 CET.2 Hospital admission costs lower in treatment group.2 | 2 |
| Pison et al. (40) | COPD | 126 | RCT | 3 mo | Malnourished patients [BMI <21 kg/m2 or FFMI measured by 50 kHz BIA <25th percentile of predicted, which corresponds to FFMI <18 kg/m2 (M) or <15 kg/m2 (F) (36, 41)] | Unsupervised cycling 3–5×/wk; elastic band exercises (3×/wk) | ONS 120 mL 3×/d | Testosterone 80 mg (M)/40 mg (F) 2×/d | “Home health education” (n = 62) | Improvements in treatment group for BMI,2 FFMI,2 Hb,2 PW,2 QIF,2 ET,2 CRQ (F only2). Survival was also better in compliant patients. | 2 |
| Baldi et al. (42) | COPD | 28 | RCT: pilot study | 12 wk (within 6-mo rehab program) | Defined as dynamic weight loss (>5% BW) <6 mo | Exercise (uploaded cycling 30 min, 2×/wk) | ONS; 4 g in 200 mL, 2–3×/d | X | Exercise (uploaded cycling 30 min, 2×/wk) (n = 14) | Increased FFMI and BW2 in treatment group. | 0 |
| Hristea et al. (43) | Renal | 21 | RCT: open-label | 6 mo | PEW according to Fouque et al. (44)3 | Intra-dialytic exercise program (cycling using cycloergometer 30 min, 3×/wk) | INS (ONS if necessary) | X | INS (ONS if necessary) (n = 11) | Treatment group reported improvement in 6MWT2 and QoL. Decline in balance for control group only. | 0 |
| Jeong et al. (45) | Renal | 138 Protein (n = 45) vs protein and exercise (n = 49) vs control | RCT | 12 mo | Not defined | Protein and exercise group only: intra-dialysis cycling 5–45 min | Protein group/protein and exercise group: intra-dialysis ONS 30 g whey mixed with 4–6 ounces of water | X | Intra-dialysis 150 g nonnutritive beverage (n = 44) | Improvements for gait/leg strength for treatment groups only. | 2 |
| Dong et al. (46) | Renal | 32 | RCT: open label | 6 mo | Not defined | RT (12 reps × 3 using leg-press machine) | Intra-dialytic ONS (480 kcal) | X | Intra-dialytic ONS (480 kcal) (n = 17) | BW2 and 1-repetition maximum2 | 2 |
| Martin-Alemañy et al. (47) | Renal | 44 | RCT | 3 mo | PEW according to Fouque et al. (44)3 | RT: adapted “exercise: a guide for people on dialysis” with 500-g ankle weights, medical resistance springs for hands and arms (2×/wk, 40 min, 30 reps ×4; ∼24 sessions) | ONS (434 kcal, 19.2 g protein and 22.8 g lipids) | X | ONS (434 kcal, 19.2 g protein and 22.8 g lipids) (n = 22) | Decrease in PEW prevalence and increases in dietary energy2/protein intake2 for both groups. Increases in BW, BMI, TSF, FM percentage, HGS, phase angle, and ALB in both groups.2 | 2 |
| Uster et al. (48) | Cancer | 58 | RCT | 12 wk | Not defined | Group cycling, strength program, and balance training (60 min 2×/wk) | INS plus supplement | X | Controls to keep “everyday habits without chasing daily PA level. ONS provided when medically indicated by treating physician” (n = 29) | Improvements in treatment group for nausea/vomiting (patient-rated symptom scale) and protein intake2 | 2 |
| Solheim et al. (49) | Cancer | 46 | RCT: feasibility | 6 wk | Cachexia: BMI <30 kg/m2 and 20% weight loss <6 mo | Aerobic 30 min, 2×/wk; resistance training 20 min, 3×/wk (home-based) | ONS (542 kcal; 30 g protein) | Ibuprofen 1200 mg/d; Ω-3 PUFAs (2 g EPA/1 g DHA) | “No nutrition, exercise or NSAIDs offered” (n = 21) | Attrition rate 11% (41/46). Good feasibility and safety profile. BW gain in treatment group and BW loss in control group. | 2 |
| Xu et al. (50) | Cancer | 59 | RCT: pilot study | 6 wk | Not defined | Supervised walking 3×/wk (protocol provided) | INS vs feeding tube | X | “Conventional medical care” (n = 28) | Lower intravenous nutritional need, wheelchair use, less decline in 6MWT2 (100-m), HGS2 (3 kg), and BW2 (2 kg) in treatment group. | 2 |
| Wen et al. (51) | Cancer | 102 | RCT | 8 wk | Loss of >5% of pre-illness or ideal BMI in previous 3 mo | X | MA 160 mg po, 2×/d | Thalidomide (50 mg po, 2×/d) | MA 160 mg po, 2×/d (n = 54) | Treatment group reported improvements in GPS and BW,2 QoL,2 appetite,2 HGS,2 fatigue,2 ECOG PS,2 IL-6,2 TNF.2 Controls also reported improvements in BW2 and appetite.2 | 2 |
| Schink et al. (52) | Cancer | 131 | Controlled pilot study | 12 wk | Not defined | WB-EMS 20 min, 2×/wk | INS | X | INS (n = 35) | Treatment group improved PF2 and PS2 only | Low |
ALB, serum albumin; BIA, bioelectrical impedance analysis; BMI, body mass index; BW, body weight; CET, cycle endurance test; COPD, chronic obstructive pulmonary disease; CRQ, chronic respiratory disease questionnaire; DHA, docosahexaenoic acid; ECOG PS, Eastern Cooperative Oncology Group Performance Status; EQ-5D-3L, EuroQoL Five Dimensions Questionnaire; EPA, eicosapentaenoic acid; ET, endurance time; FFMI, fat-free mass index; FM, fat mass; F, female; GPS, Glasgow Prognostic Score; HADS, Hospital Anxiety and Depression Scale; Hb, haemoglobin; HDL, high-density lipoprotein; HGS, handgrip strength; IL-6, Interleukin-6; INS, individualized nutritional support; M, male; MA, megestrol acetate; MIN, minutes; NSAIDs, nonsteroidal anti-inflammatory drugs; ONS, oral nutritional supplement; PA, physical activity; PEW, protein-energy wasting; PF, physical functioning; PS, performance status; PW, peak workload; QA, quality assessment; QIF, quadriceps isometric force; QoL, quality of Life; RCT, randomized controlled trial; RT, resistance training; TNF, tumor necrosis factor; TSF, tricep skinfold thickness; UWL, unintentional weight loss; WB-EMS, whole-body electro-myostimulation; 6MWT, 6-Minute Walk Test; Ω-3 PUFAs, omega-3 polyunsaturated fatty acids.
P < 0.05 is considered significant.
Three of 4 of the following listed categories and at least 1 test of the following—1) albumin: <3.8 g/100 mL; 2) BMI <23 kg/m2; UWL over time: 5% over 3 mo or 10% over 6 mo or total body fat percentage <10%; 3) muscle mass: reduced muscle mass 5% over 3 mo or 10% over 6 mo or reduced mid-arm circumference area or creatinine appearance; and 4) dietary intake: unintentional low dietary energy intake <1 g/(kg of ideal weight/d) for at least 2 mo, unintentional low dietary energy intake <30 kcal/(kg of ideal weight/d) for at least 2 mo.