Caccialanza 2015.

Study characteristics
Methods	RCT. Parallel design with 2 arms. Duration: 12 months. Location: single centre in Italy.
Participants	Inclusion criteria: amyloidosis adult outpatients who were treatment naïve and able to provide written informed consent. Exclusion criteria: indication to autologous stem cell transplantation, in need of starting or ongoing dialysis or ongoing artificial nutrition, presence of ascites or relevant peripheral oedema. Number randomised: 144 participants; intervention n = 72, control n = 72. Gender split: intervention group 62% male; control group 60% male. Age: mean (SD) intervention 65.4 (10.5) years; control 64.8 (9.7) years. Nutritional status: BMI at baseline, mean (SD): intervention group 24.6 (3.3) and control group 25.4 (4.1). Unintentional weight loss, median (IQR): intervention group 3.0 (0.0 – 6.0) kg and control group 4.0 (0.3 – 7.0) kg.
Interventions	Intervention: participants received dietary advice plus ONS if required in the form off personalized dietary prescription (modelled on personal eating patterns and preferences, to satisfy estimated protein–calorie requirements* and based primarily on the use of regular foods; oral nutrition supplements were prescribed when necessary) plus dietetic advice from a registered dietitian every 3 weeks by telephone and every 3 months face‐to‐face. Control: participants received no dietary advice and no ONS in the form of written general nutritional advice aimed at maintaining or recovering body weight, participants were allowed to ad libitum food intake, without fixed prescription of oral nutritional supplements; if participants had questions concerning nutrition, they were advised by the Amyloidosis Center’s attending physician or the nurses, but not by the professional dietitian. *Energy requirements: Harris‐Benedict equation x 1.5, protein requirements 1.1 g/kg of actual body weight in case of normal kidney function; in the presence of kidney involvement, adjustments were performed according to available guidelines and laboratory data.
Outcomes	Body weight*, MAMC, energy intake (% of participants reaching requirements), QoL (SF‐36, only subscales), mortality*.
Publication details	Language: English. Funding: the Fondazione IRCCS Policlinico San Matteo (Pavia,Italy) and partly supported by grants from "Associazione Italiana per la Ricerca sul Cancro ‐ Special Program Molecular Clinical Oncology 5 per mille" (grant n. 9965) and Cariplo Foundation (grant no. 2013‐0964). Publication status: peer‐reviewed journal.
Notes	Not all participants were malnourished at baseline. QoL data could not be used because only subscales were reported.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: a computer‐generated randomization list (randomized blocks) was used. Accordingly, eligible participants were randomized (1:1) to either the nutritional counselling (NC) or usual care (UC) group."
Allocation concealment (selection bias)	Unclear risk	Not described.
Blinding (performance bias and detection bias) Clinical outcomes	Low risk	Stated as open‐label, meaning that both researchers and participants know which treatment is being administered. However, this is unlikely to influence mortality rate.
Blinding (performance bias and detection bias) Functional outcomes	High risk	Stated as open‐label, meaning that both researchers and participants know which treatment is being administered. Functional outcomes could have been influenced by lack of blinding.
Blinding (performance bias and detection bias) Nutritional outcomes	High risk	Stated as open‐label, meaning that both researchers and participants know which treatment is being administered. Nutritional outcomes could have been influenced by lack of blinding.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Not blinded and likely that researchers and participants were aware of group allocation as this was a nutritional intervention. It is possible that assessment of some outcomes was influenced by lack of blinding
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Judged to be unclear because low risk for clinical outcomes and high risk for functional and nutritional outcomes.
Incomplete outcome data (attrition bias) All outcomes	High risk	Overall attrition 84/144 (58%) participants; intervention group 51/72 (71%), control group 33/72 (46%), therefore amounts judged to be unbalanced between groups. High mortality rates due to complexity of the group. Assessed at 3 months: intervention n = 56, control n = 47. Assessed at 12 months: intervention n = 39, control n = 21. 41 did not attend the first follow‐up visit at 3 months (intervention group n = 16, control group n = 25). Most drop outs were caused by death: intervention n = 20, control n = 33.
Selective reporting (reporting bias)	Low risk	Protocol identified Clintrials NCT02055534 all planned outcomes were reported.
Other bias	Low risk	Baseline characteristics were similar between groups.