Trial Outcomes & Findings for Skin Autofluorescence as a Risk Marker in People Receiving Dialysis. (NCT NCT02878317)

NCT ID: NCT02878317

Last Updated: 2024-12-10

Results Overview

Skin autolfuorescence (SAF) was measured after 6 months of intensive dietetic advice and nutritional support with a validated Autofluorescence Reader (AGE) Standard Unit (SU), version 2.4.3. The AGE Reader SU directs an ultraviolet excitation light through an illumination window of approximately 1 cm2 on a skin area of the volar surface of the forearm at approximately 10 cm below the elbow. The AGE Reader then measures the amount of emitted light that is reflected back from the skin using a spectrometer and a 200-µm glass fiber. SAF is calculated as the ratio between emission and excitation and is expressed as arbitrary units (AU). Three measurements were conducted and the mean value of these was used for statistical analysis. The reference value of SAF for the age group of 60-70 years is 2.5±0.6 AU.

• Recruitment status: COMPLETED
• Target enrollment: 81 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2024-12-10

Participant Flow

Study 1: Participant recruitment began in September 2016. All baseline data and measurements were collected and performed between September 2016 and August 2017. Once recruited, all participants were followed-up for up to five years. Study 2: Participant recruitment began in December 2017. All baseline data and measurements were collected and performed between December 2017 and June 2018. Once recruited, all participants were followed-up for up to 24 months.

Participant milestones

Measure	Study 2 - Non Randomised Proof of Principle Study Malnourished participants received individualized nutritional advice and support formulated and delivered by experienced dietitians consisting of food fortification recommendations and oral nutritional supplementation aiming to achieve estimated nutritional requirements (i.e. energy \[30-35 kcal/kg/day\] and protein intake \[1.1-1.2 g/kg/day\]). Food fortification involved enhancing the energy and protein content of meals and snacks without increasing the portion sizes of foods. Advice was individualized according to patient needs and food preferences. Oral nutritional supplements included Fortisip Compact (2.4 kcal/ml), Fortisip (1.5 kcal/ml) and Fortijuice (1.5 kcal/ml) (Nutricia Advanced Medical Nutrition®, Wiltshire, United Kingdom), as well as Renapro® shot (Stanningly Pharma, BioCity, Pennyfoot Street, Nottingham, United Kingdom) and Fresubin® 5kcal Shot (Fresenius Kabi Ireland, Balbriggan, Dublin, Ireland). Participants received precise oral and written instructions on how and when to take the supplements and how to follow the food fortification advice provided. Participants were closely monitored by the dietitian at least once a week to encourage adherence to nutritional advice, and 24-hour dietary recalls were also conducted to ensure compliance with the advice provided. Each participant was also reviewed quarterly with the clinical lead renal dietitian in order to modify the dietetic advice, if required.	Historical Control Group From Study 1 Participants on dialysis with malnutrition taken from Study 1, who were seen by their usual dietitian once a month and received standard nutritional counselling.
Overall Study STARTED	32	49
Overall Study COMPLETED	28	49
Overall Study NOT COMPLETED	4	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Skin Autofluorescence as a Risk Marker in People Receiving Dialysis.

Baseline characteristics by cohort

Measure	Study 2 n=28 Participants Baseline data is for the 28 malnourished participants who completed 6 months of follow-up	Historical Control Group - Study 1 n=49 Participants A historical control group of malnourished persons on dialysis (n=41 haemodialysis and 8 peritoneal dialysis) taken from Study 1 (observational study).	Total n=77 Participants Total of all reporting groups
Age, Continuous	65 years n=5 Participants	63 years n=7 Participants	64 years n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	26 Participants n=7 Participants	40 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	23 Participants n=7 Participants	37 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	24 Participants n=5 Participants	43 Participants n=7 Participants	67 Participants n=5 Participants
Race (NIH/OMB) More than one race	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Serum albumin	30.0 g/L n=5 Participants	32.0 g/L n=7 Participants	31.0 g/L n=5 Participants
Dietary AGE intake	13823 Kilounits/day n=5 Participants	11940 Kilounits/day n=7 Participants	12882 Kilounits/day n=5 Participants
Energy intake	20.9 kcal/kg/day n=5 Participants	17.9 kcal/kg/day n=7 Participants	19.4 kcal/kg/day n=5 Participants
Protein intake	0.7 g/kg/day n=5 Participants	0.8 g/kg/day n=7 Participants	0.75 g/kg/day n=5 Participants
Skin autofluorescence	3.8 Arbitrary units STANDARD_DEVIATION 0.7 • n=5 Participants	3.5 Arbitrary units STANDARD_DEVIATION 0.9 • n=7 Participants	3.7 Arbitrary units STANDARD_DEVIATION 0.8 • n=5 Participants
Handgrip strength	15.2 kg n=5 Participants	17.3 kg n=7 Participants	16.3 kg n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Skin autolfuorescence (SAF) was measured after 6 months of intensive dietetic advice and nutritional support with a validated Autofluorescence Reader (AGE) Standard Unit (SU), version 2.4.3. The AGE Reader SU directs an ultraviolet excitation light through an illumination window of approximately 1 cm2 on a skin area of the volar surface of the forearm at approximately 10 cm below the elbow. The AGE Reader then measures the amount of emitted light that is reflected back from the skin using a spectrometer and a 200-µm glass fiber. SAF is calculated as the ratio between emission and excitation and is expressed as arbitrary units (AU). Three measurements were conducted and the mean value of these was used for statistical analysis. The reference value of SAF for the age group of 60-70 years is 2.5±0.6 AU.

Outcome measures

Measure	Study 2 - Non Randomised Proof of Principle Study n=28 Participants Malnourished participants received individualized nutritional advice and support formulated and delivered by experienced dietitians consisting of food fortification recommendations and oral nutritional supplementation aiming to achieve estimated nutritional requirements (i.e. energy \[30-35 kcal/kg/day\] and protein intake \[1.1-1.2 g/kg/day\]). Food fortification involved enhancing the energy and protein content of meals and snacks without increasing the portion sizes of foods. Advice was individualized according to patient needs and food preferences. Oral nutritional supplements included Fortisip Compact (2.4 kcal/ml), Fortisip (1.5 kcal/ml) and Fortijuice (1.5 kcal/ml) (Nutricia Advanced Medical Nutrition®, Wiltshire, United Kingdom), as well as Renapro® shot (Stanningly Pharma, BioCity, Pennyfoot Street, Nottingham, United Kingdom) and Fresubin® 5kcal Shot (Fresenius Kabi Ireland, Balbriggan, Dublin, Ireland). Participants received precise oral and written instructions on how and when to take the supplements and how to follow the food fortification advice provided. Participants were closely monitored by the dietitian at least once a week to encourage adherence to nutritional advice, and 24-hour dietary recalls were also conducted to ensure compliance with the advice provided. Each participant was also reviewed quarterly with the clinical lead renal dietitian in order to modify the dietetic advice, if required.	Historical Control Group From Study 1 n=49 Participants Participants on dialysis with malnutrition taken from Study 1, who were seen by their usual dietitian once a month and received standard nutritional counselling.
Skin Autofluorescence Levels at 6 Months	3.7 Arbitrary units Standard Deviation 0.7	3.8 Arbitrary units Standard Deviation 1.2

SECONDARY outcome

Timeframe: 6 months

Energy (calorie) intake after 6 months of intensive dietetic advice and nutritional support.

Outcome measures

Measure	Study 2 - Non Randomised Proof of Principle Study n=28 Participants Malnourished participants received individualized nutritional advice and support formulated and delivered by experienced dietitians consisting of food fortification recommendations and oral nutritional supplementation aiming to achieve estimated nutritional requirements (i.e. energy \[30-35 kcal/kg/day\] and protein intake \[1.1-1.2 g/kg/day\]). Food fortification involved enhancing the energy and protein content of meals and snacks without increasing the portion sizes of foods. Advice was individualized according to patient needs and food preferences. Oral nutritional supplements included Fortisip Compact (2.4 kcal/ml), Fortisip (1.5 kcal/ml) and Fortijuice (1.5 kcal/ml) (Nutricia Advanced Medical Nutrition®, Wiltshire, United Kingdom), as well as Renapro® shot (Stanningly Pharma, BioCity, Pennyfoot Street, Nottingham, United Kingdom) and Fresubin® 5kcal Shot (Fresenius Kabi Ireland, Balbriggan, Dublin, Ireland). Participants received precise oral and written instructions on how and when to take the supplements and how to follow the food fortification advice provided. Participants were closely monitored by the dietitian at least once a week to encourage adherence to nutritional advice, and 24-hour dietary recalls were also conducted to ensure compliance with the advice provided. Each participant was also reviewed quarterly with the clinical lead renal dietitian in order to modify the dietetic advice, if required.	Historical Control Group From Study 1 n=49 Participants Participants on dialysis with malnutrition taken from Study 1, who were seen by their usual dietitian once a month and received standard nutritional counselling.
Energy Intake at 6 Months.	30.1 Kcal/kg/day Interval 24.9 to 35.9	18.9 Kcal/kg/day Interval 15.1 to 26.9

SECONDARY outcome

Timeframe: 6 months

The 7-point scale Subjective Global Assessment (SGA, gold standard for nutritional status assessment in the dialysis population) was used to evaluate nutritional status at 6 months after intensive dietetic advice and nutritional support. The SGA score ranges from 1-7. Nutritional status can be classified into normal nutritional status (scores of 6 or 7), mild-moderate malnutrition (scores of 3-5), or severe malnutrition (scores of 1 or 2).

Outcome measures

Measure	Study 2 - Non Randomised Proof of Principle Study n=28 Participants Malnourished participants received individualized nutritional advice and support formulated and delivered by experienced dietitians consisting of food fortification recommendations and oral nutritional supplementation aiming to achieve estimated nutritional requirements (i.e. energy \[30-35 kcal/kg/day\] and protein intake \[1.1-1.2 g/kg/day\]). Food fortification involved enhancing the energy and protein content of meals and snacks without increasing the portion sizes of foods. Advice was individualized according to patient needs and food preferences. Oral nutritional supplements included Fortisip Compact (2.4 kcal/ml), Fortisip (1.5 kcal/ml) and Fortijuice (1.5 kcal/ml) (Nutricia Advanced Medical Nutrition®, Wiltshire, United Kingdom), as well as Renapro® shot (Stanningly Pharma, BioCity, Pennyfoot Street, Nottingham, United Kingdom) and Fresubin® 5kcal Shot (Fresenius Kabi Ireland, Balbriggan, Dublin, Ireland). Participants received precise oral and written instructions on how and when to take the supplements and how to follow the food fortification advice provided. Participants were closely monitored by the dietitian at least once a week to encourage adherence to nutritional advice, and 24-hour dietary recalls were also conducted to ensure compliance with the advice provided. Each participant was also reviewed quarterly with the clinical lead renal dietitian in order to modify the dietetic advice, if required.	Historical Control Group From Study 1 n=49 Participants Participants on dialysis with malnutrition taken from Study 1, who were seen by their usual dietitian once a month and received standard nutritional counselling.
Nutritional Status at 6 Months	5.0 score on a scale Interval 5.0 to 6.0	5.0 score on a scale Interval 3.0 to 7.0

SECONDARY outcome

Timeframe: 6 months

Dietary AGE intake after 6 months of intensive dietetic advice and nutritional support

Outcome measures

Measure	Study 2 - Non Randomised Proof of Principle Study n=28 Participants Malnourished participants received individualized nutritional advice and support formulated and delivered by experienced dietitians consisting of food fortification recommendations and oral nutritional supplementation aiming to achieve estimated nutritional requirements (i.e. energy \[30-35 kcal/kg/day\] and protein intake \[1.1-1.2 g/kg/day\]). Food fortification involved enhancing the energy and protein content of meals and snacks without increasing the portion sizes of foods. Advice was individualized according to patient needs and food preferences. Oral nutritional supplements included Fortisip Compact (2.4 kcal/ml), Fortisip (1.5 kcal/ml) and Fortijuice (1.5 kcal/ml) (Nutricia Advanced Medical Nutrition®, Wiltshire, United Kingdom), as well as Renapro® shot (Stanningly Pharma, BioCity, Pennyfoot Street, Nottingham, United Kingdom) and Fresubin® 5kcal Shot (Fresenius Kabi Ireland, Balbriggan, Dublin, Ireland). Participants received precise oral and written instructions on how and when to take the supplements and how to follow the food fortification advice provided. Participants were closely monitored by the dietitian at least once a week to encourage adherence to nutritional advice, and 24-hour dietary recalls were also conducted to ensure compliance with the advice provided. Each participant was also reviewed quarterly with the clinical lead renal dietitian in order to modify the dietetic advice, if required.	Historical Control Group From Study 1 n=49 Participants Participants on dialysis with malnutrition taken from Study 1, who were seen by their usual dietitian once a month and received standard nutritional counselling.
Dietary Advanced Glycation End-products (AGE) Intake at 6 Months	19074 Kilounits/day Interval 13372.0 to 27340.0	14697 Kilounits/day Interval 9427.0 to 19071.0

SECONDARY outcome

Timeframe: 6 months

Protein intake after 6 months of intensive dietetic advice and nutritional support.

Outcome measures

Measure	Study 2 - Non Randomised Proof of Principle Study n=28 Participants Malnourished participants received individualized nutritional advice and support formulated and delivered by experienced dietitians consisting of food fortification recommendations and oral nutritional supplementation aiming to achieve estimated nutritional requirements (i.e. energy \[30-35 kcal/kg/day\] and protein intake \[1.1-1.2 g/kg/day\]). Food fortification involved enhancing the energy and protein content of meals and snacks without increasing the portion sizes of foods. Advice was individualized according to patient needs and food preferences. Oral nutritional supplements included Fortisip Compact (2.4 kcal/ml), Fortisip (1.5 kcal/ml) and Fortijuice (1.5 kcal/ml) (Nutricia Advanced Medical Nutrition®, Wiltshire, United Kingdom), as well as Renapro® shot (Stanningly Pharma, BioCity, Pennyfoot Street, Nottingham, United Kingdom) and Fresubin® 5kcal Shot (Fresenius Kabi Ireland, Balbriggan, Dublin, Ireland). Participants received precise oral and written instructions on how and when to take the supplements and how to follow the food fortification advice provided. Participants were closely monitored by the dietitian at least once a week to encourage adherence to nutritional advice, and 24-hour dietary recalls were also conducted to ensure compliance with the advice provided. Each participant was also reviewed quarterly with the clinical lead renal dietitian in order to modify the dietetic advice, if required.	Historical Control Group From Study 1 n=49 Participants Participants on dialysis with malnutrition taken from Study 1, who were seen by their usual dietitian once a month and received standard nutritional counselling.
Protein Intake at 6 Months.	1.1 g/kg/day Interval 0.8 to 1.2	0.8 g/kg/day Interval 0.6 to 1.0

SECONDARY outcome

Timeframe: 6 months

Serum albumin levels after 6 months of intensive dietetic advice and nutritional support.

Outcome measures

Measure	Study 2 - Non Randomised Proof of Principle Study n=28 Participants Malnourished participants received individualized nutritional advice and support formulated and delivered by experienced dietitians consisting of food fortification recommendations and oral nutritional supplementation aiming to achieve estimated nutritional requirements (i.e. energy \[30-35 kcal/kg/day\] and protein intake \[1.1-1.2 g/kg/day\]). Food fortification involved enhancing the energy and protein content of meals and snacks without increasing the portion sizes of foods. Advice was individualized according to patient needs and food preferences. Oral nutritional supplements included Fortisip Compact (2.4 kcal/ml), Fortisip (1.5 kcal/ml) and Fortijuice (1.5 kcal/ml) (Nutricia Advanced Medical Nutrition®, Wiltshire, United Kingdom), as well as Renapro® shot (Stanningly Pharma, BioCity, Pennyfoot Street, Nottingham, United Kingdom) and Fresubin® 5kcal Shot (Fresenius Kabi Ireland, Balbriggan, Dublin, Ireland). Participants received precise oral and written instructions on how and when to take the supplements and how to follow the food fortification advice provided. Participants were closely monitored by the dietitian at least once a week to encourage adherence to nutritional advice, and 24-hour dietary recalls were also conducted to ensure compliance with the advice provided. Each participant was also reviewed quarterly with the clinical lead renal dietitian in order to modify the dietetic advice, if required.	Historical Control Group From Study 1 n=49 Participants Participants on dialysis with malnutrition taken from Study 1, who were seen by their usual dietitian once a month and received standard nutritional counselling.
Serum Albumin Levels at 6 Months	31.5 g/L Interval 30.0 to 34.0	31.0 g/L Interval 27.0 to 34.5

SECONDARY outcome

Timeframe: 6 months

Handgrip strength after 6 months of intensive dietetic advice and nutritional support.

Outcome measures

Measure	Study 2 - Non Randomised Proof of Principle Study n=28 Participants Malnourished participants received individualized nutritional advice and support formulated and delivered by experienced dietitians consisting of food fortification recommendations and oral nutritional supplementation aiming to achieve estimated nutritional requirements (i.e. energy \[30-35 kcal/kg/day\] and protein intake \[1.1-1.2 g/kg/day\]). Food fortification involved enhancing the energy and protein content of meals and snacks without increasing the portion sizes of foods. Advice was individualized according to patient needs and food preferences. Oral nutritional supplements included Fortisip Compact (2.4 kcal/ml), Fortisip (1.5 kcal/ml) and Fortijuice (1.5 kcal/ml) (Nutricia Advanced Medical Nutrition®, Wiltshire, United Kingdom), as well as Renapro® shot (Stanningly Pharma, BioCity, Pennyfoot Street, Nottingham, United Kingdom) and Fresubin® 5kcal Shot (Fresenius Kabi Ireland, Balbriggan, Dublin, Ireland). Participants received precise oral and written instructions on how and when to take the supplements and how to follow the food fortification advice provided. Participants were closely monitored by the dietitian at least once a week to encourage adherence to nutritional advice, and 24-hour dietary recalls were also conducted to ensure compliance with the advice provided. Each participant was also reviewed quarterly with the clinical lead renal dietitian in order to modify the dietetic advice, if required.	Historical Control Group From Study 1 n=49 Participants Participants on dialysis with malnutrition taken from Study 1, who were seen by their usual dietitian once a month and received standard nutritional counselling.
Handgrip Strength at 6 Months	16.7 kg Interval 10.6 to 24.7	18.3 kg Interval 12.4 to 26.3

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

The Short Form-36 (SF-36) physical component score (PCS) was calculated after 6 months of intensive dietetic advice and nutritional support according to well-defined guidelines as follows: 1) recoding of 10 questions of the SF-36 survey; 2) calculation of raw scores for each of the eight health state domains of the SF-36 survey; 3) transformation of raw scores into a 0-100 scale; 4) standardisation of the transformed scales using a z-score transformation and the means and standard deviations from the general United Kingdom (UK) population; 5) calculation of the PCS by multiplying each scale z-score by their respective physical factor score coefficient and summing the eight products; and 6) the resulting sum is multiplied by 10 and added to 50 to linearly transform the PCS to the T-score metric, which has a mean of 50 and a standard deviation of 10 for the general UK population. A PCS above or below 50 is therefore indicative of better or worse physical health, respectively.

Outcome measures

Measure	Study 2 - Non Randomised Proof of Principle Study n=28 Participants Malnourished participants received individualized nutritional advice and support formulated and delivered by experienced dietitians consisting of food fortification recommendations and oral nutritional supplementation aiming to achieve estimated nutritional requirements (i.e. energy \[30-35 kcal/kg/day\] and protein intake \[1.1-1.2 g/kg/day\]). Food fortification involved enhancing the energy and protein content of meals and snacks without increasing the portion sizes of foods. Advice was individualized according to patient needs and food preferences. Oral nutritional supplements included Fortisip Compact (2.4 kcal/ml), Fortisip (1.5 kcal/ml) and Fortijuice (1.5 kcal/ml) (Nutricia Advanced Medical Nutrition®, Wiltshire, United Kingdom), as well as Renapro® shot (Stanningly Pharma, BioCity, Pennyfoot Street, Nottingham, United Kingdom) and Fresubin® 5kcal Shot (Fresenius Kabi Ireland, Balbriggan, Dublin, Ireland). Participants received precise oral and written instructions on how and when to take the supplements and how to follow the food fortification advice provided. Participants were closely monitored by the dietitian at least once a week to encourage adherence to nutritional advice, and 24-hour dietary recalls were also conducted to ensure compliance with the advice provided. Each participant was also reviewed quarterly with the clinical lead renal dietitian in order to modify the dietetic advice, if required.	Historical Control Group From Study 1 n=48 Participants Participants on dialysis with malnutrition taken from Study 1, who were seen by their usual dietitian once a month and received standard nutritional counselling.
Health-related Quality of Life, Short Form-36 Physical Component Score	17.2 score on a scale Interval 8.1 to 26.9	15.9 score on a scale Interval 10.4 to 22.8

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

The Short Form-36 (SF-36) mental component score (MCS) was calculated after 6 months of intensive dietetic advice and nutritional support according to well-defined guidelines as follows: 1) recoding of 10 questions of the SF-36 survey; 2) calculation of raw scores for each of the eight health state domains of the SF-36 survey; 3) transformation of raw scores into a 0-100 scale; 4) standardisation of the transformed scales using a z-score transformation and the means and standard deviations from the general United Kingdom (UK) population; 5) calculation of the MCS by multiplying each scale z-score by their respective mental factor score coefficient and summing the eight products; and 6) the resulting sum is multiplied by 10 and added to 50 to linearly transform the MCS to the T-score metric, which has a mean of 50 and a standard deviation of 10 for the general UK population. A MCS score above or below 50 is therefore indicative of better or worse mental health, respectively.

Outcome measures

Measure	Study 2 - Non Randomised Proof of Principle Study n=28 Participants Malnourished participants received individualized nutritional advice and support formulated and delivered by experienced dietitians consisting of food fortification recommendations and oral nutritional supplementation aiming to achieve estimated nutritional requirements (i.e. energy \[30-35 kcal/kg/day\] and protein intake \[1.1-1.2 g/kg/day\]). Food fortification involved enhancing the energy and protein content of meals and snacks without increasing the portion sizes of foods. Advice was individualized according to patient needs and food preferences. Oral nutritional supplements included Fortisip Compact (2.4 kcal/ml), Fortisip (1.5 kcal/ml) and Fortijuice (1.5 kcal/ml) (Nutricia Advanced Medical Nutrition®, Wiltshire, United Kingdom), as well as Renapro® shot (Stanningly Pharma, BioCity, Pennyfoot Street, Nottingham, United Kingdom) and Fresubin® 5kcal Shot (Fresenius Kabi Ireland, Balbriggan, Dublin, Ireland). Participants received precise oral and written instructions on how and when to take the supplements and how to follow the food fortification advice provided. Participants were closely monitored by the dietitian at least once a week to encourage adherence to nutritional advice, and 24-hour dietary recalls were also conducted to ensure compliance with the advice provided. Each participant was also reviewed quarterly with the clinical lead renal dietitian in order to modify the dietetic advice, if required.	Historical Control Group From Study 1 n=48 Participants Participants on dialysis with malnutrition taken from Study 1, who were seen by their usual dietitian once a month and received standard nutritional counselling.
Health-related Quality of Life, Short Form-36 Mental Component Score	47.5 score on a scale Interval 38.5 to 57.3	41.6 score on a scale Interval 30.6 to 49.9

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

EQ5D HSS after 6 months of intensive dietetic advice and nutritional support. The HSS ranges from -0.285 (for the worst health state) to 1 (for the best health state).

Outcome measures

Measure	Study 2 - Non Randomised Proof of Principle Study n=28 Participants Malnourished participants received individualized nutritional advice and support formulated and delivered by experienced dietitians consisting of food fortification recommendations and oral nutritional supplementation aiming to achieve estimated nutritional requirements (i.e. energy \[30-35 kcal/kg/day\] and protein intake \[1.1-1.2 g/kg/day\]). Food fortification involved enhancing the energy and protein content of meals and snacks without increasing the portion sizes of foods. Advice was individualized according to patient needs and food preferences. Oral nutritional supplements included Fortisip Compact (2.4 kcal/ml), Fortisip (1.5 kcal/ml) and Fortijuice (1.5 kcal/ml) (Nutricia Advanced Medical Nutrition®, Wiltshire, United Kingdom), as well as Renapro® shot (Stanningly Pharma, BioCity, Pennyfoot Street, Nottingham, United Kingdom) and Fresubin® 5kcal Shot (Fresenius Kabi Ireland, Balbriggan, Dublin, Ireland). Participants received precise oral and written instructions on how and when to take the supplements and how to follow the food fortification advice provided. Participants were closely monitored by the dietitian at least once a week to encourage adherence to nutritional advice, and 24-hour dietary recalls were also conducted to ensure compliance with the advice provided. Each participant was also reviewed quarterly with the clinical lead renal dietitian in order to modify the dietetic advice, if required.	Historical Control Group From Study 1 n=48 Participants Participants on dialysis with malnutrition taken from Study 1, who were seen by their usual dietitian once a month and received standard nutritional counselling.
Health-related Quality of Life, European QoL-5 Dimensions (EQ5D) Health State Score (HSS)	0.485 score on a scale Interval 0.297 to 0.741	0.470 score on a scale Interval 0.198 to 0.699

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

EQ5D VAS after 6 months of intensive dietetic advice and support. The VAS uses a thermometer-like scale numbered from 0 to 100 to grade the current health status of individuals; the higher the VAS the better the health state.

Outcome measures

Measure	Study 2 - Non Randomised Proof of Principle Study n=28 Participants Malnourished participants received individualized nutritional advice and support formulated and delivered by experienced dietitians consisting of food fortification recommendations and oral nutritional supplementation aiming to achieve estimated nutritional requirements (i.e. energy \[30-35 kcal/kg/day\] and protein intake \[1.1-1.2 g/kg/day\]). Food fortification involved enhancing the energy and protein content of meals and snacks without increasing the portion sizes of foods. Advice was individualized according to patient needs and food preferences. Oral nutritional supplements included Fortisip Compact (2.4 kcal/ml), Fortisip (1.5 kcal/ml) and Fortijuice (1.5 kcal/ml) (Nutricia Advanced Medical Nutrition®, Wiltshire, United Kingdom), as well as Renapro® shot (Stanningly Pharma, BioCity, Pennyfoot Street, Nottingham, United Kingdom) and Fresubin® 5kcal Shot (Fresenius Kabi Ireland, Balbriggan, Dublin, Ireland). Participants received precise oral and written instructions on how and when to take the supplements and how to follow the food fortification advice provided. Participants were closely monitored by the dietitian at least once a week to encourage adherence to nutritional advice, and 24-hour dietary recalls were also conducted to ensure compliance with the advice provided. Each participant was also reviewed quarterly with the clinical lead renal dietitian in order to modify the dietetic advice, if required.	Historical Control Group From Study 1 n=48 Participants Participants on dialysis with malnutrition taken from Study 1, who were seen by their usual dietitian once a month and received standard nutritional counselling.
Health-related Quality of Life, European QoL-5 Dimensions (EQ5D) Visual Analogue Score (VAS)	45 score on a scale Interval 27.0 to 60.0	50 score on a scale Interval 25.0 to 69.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

Population: A total of 32 dialysis patients were enrolled at baseline in Study 2. Four patients did not complete the study protocol. Twenty eight patients completed 6 months of intervention and were therefore included in the final analysis. Historical controls were selected from a previous cohort of 151 dialysis patients. Of these, 56 were classified as being malnourished at baseline. Forty nine patients completed 6 months of follow-up and were included in the final analysis.

The total number of deaths during follow up was recorded at 6 months.

Outcome measures

Measure	Study 2 - Non Randomised Proof of Principle Study n=32 Participants Malnourished participants received individualized nutritional advice and support formulated and delivered by experienced dietitians consisting of food fortification recommendations and oral nutritional supplementation aiming to achieve estimated nutritional requirements (i.e. energy \[30-35 kcal/kg/day\] and protein intake \[1.1-1.2 g/kg/day\]). Food fortification involved enhancing the energy and protein content of meals and snacks without increasing the portion sizes of foods. Advice was individualized according to patient needs and food preferences. Oral nutritional supplements included Fortisip Compact (2.4 kcal/ml), Fortisip (1.5 kcal/ml) and Fortijuice (1.5 kcal/ml) (Nutricia Advanced Medical Nutrition®, Wiltshire, United Kingdom), as well as Renapro® shot (Stanningly Pharma, BioCity, Pennyfoot Street, Nottingham, United Kingdom) and Fresubin® 5kcal Shot (Fresenius Kabi Ireland, Balbriggan, Dublin, Ireland). Participants received precise oral and written instructions on how and when to take the supplements and how to follow the food fortification advice provided. Participants were closely monitored by the dietitian at least once a week to encourage adherence to nutritional advice, and 24-hour dietary recalls were also conducted to ensure compliance with the advice provided. Each participant was also reviewed quarterly with the clinical lead renal dietitian in order to modify the dietetic advice, if required.	Historical Control Group From Study 1 n=56 Participants Participants on dialysis with malnutrition taken from Study 1, who were seen by their usual dietitian once a month and received standard nutritional counselling.
Deaths/All-cause Mortality	3 participants	5 participants

Adverse Events

Study 2

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Historical Control Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Professor Maarten Taal

University of Nottingham

Phone: 01332 224618

Email: m.taal@nottingham.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place