Oral Nutrition Supplements vs. Energy- and Protein Dense in Between Meal Snacks, Weight Changes and Functional Capacity in Chronic Obstructive Pulmonary Disease; Randomized Controlled Dietary Intervention
Phase: NA
Conditions: Malnutrition
Sponsor: University of Iceland

ID: COPD-141316051       
 
 
 
 
 
NCT02251496   
 
 
 
 
 
 
COPD: Oral Nutrition Supplements vs. Energy- 
and Protein Dense in Between Meal Snacks.      
 
 
 
 
 
 
 
 
 
 
 
Áróra Rós Ingadóttir   
 
 
 
 
 
12/23/2020 

METHODS 
Study design and participants 
This study was a randomised trial and registered at clinicaltrials.gov on September 25, 2014. 
ClinicalTrials.gov identifier: NCT02251496. The study was approved by the National 
Bioethics Committee (VSN14-066-S1), Chief medical officer Landspitali (LSH 68-14) and 
Data Protection Authority (2014/908) and conducted in line with the Declaration of Helsinki. 
The study follows the CONSORT 2010 statement: extension to randomised pilot and 
feasibility trials. (Eldridge et al., 2016)  
Patients with a clinical diagnoses of COPD who had been recently admitted to the 
Department of Respiratory Medicine at Landspitali University Hospital were screened for 
possible nutritional risk (score ≥4) by a trained researcher using a validated nutritional 
screening tool. (Ingadottir et al.; Thorsdottir, Gunnarsdottir, & Eriksen, 2001) The Icelandic 
Simple Screening (ISS) used is recommended by the clinical guidelines for hospital nutrition 
at Landspitali (Friðriksdóttir, 2011) and has been validated against a full nutritional 
assessment in COPD patients (Thorsdottir et al., 2001) and predicts mortality in COPD 
patients. (Ingadottir et al.) ISS gathers information on BMI, unintentional weight loss, age, co-
morbidities, recent hospitalisation and a range of symptoms that impact nutritional intake 
during the last weeks or months (vomiting, diarrhoea, loss of appetite or nausea, difficulties in 
chewing or swallowing).  
All eligible patients who were able to eat orally, and had an anticipated length of 
hospitalisation of >3 days were invited to participate in the study. The most common reason 
for admission was acute exacerbation of COPD. Written informed consent was obtained from 
all participants.  
Patients diagnosed with cancer, dysphagia, food allergy or intolerance and anatomical 
obstructions preventing oral food intake were excluded. Patients not able to sign informed 
consent due to cognitive issues were also excluded.  
Socio-demographic data (age, gender and smoking status) were collected from 
electronic medical records SAGA (TM software 3.1.39.9).  
Randomisation and masking 
Eligible patients were randomly assigned in a 1:1 ratio to either an ONS group (ONS) or 
snacks group. Random sequence generation was performed using randomisation codes 
produced by Microsoft Excel for Windows 2007. Randomisation, allocation of patients to 
groups, nutritional intervention and outcome assessments were performed by one researcher 

(ARI). Due to the nature of the intervention it was not possible to perform a blinded study. 
Randomisation took place after screening for nutritional risk and prior to baseline assessment.  
Procedures 
This study was originally designed as a randomized trial to investigate the effects of snacks on 
body weight and QoL in COPD patients compared to ONS with a planned enrolment of 200 
subjects (ClinicalTrials.gov, number NCT02251496). Despite screening 492 subjects only 76 
subjects were eligible indicating that recruitment is challenging in this population and clinical 
setting.  Recruitment rates were lower than expected which led to a change in the study 
protocol to a randomised feasibility trial as funding was limited to three years. One reason for 
low recruitment rates might be over strict inclusion criteria. More details on study recruitment 
are provided in the results. 
Nutritional screening was undertaken on admission using the validated screening tool 
as recommended for use at the Landspitali. (Friðriksdóttir, 2011; Ingadottir et al.; Thorsdottir 
et al., 2001) A total score of ≥4 is considered ‘at nutritional risk’. 
After providing informed consent, subjects were randomly allocated to one of two 
groups. Subjects in group 1 were provided with ONS and subjects in group 2 were provided 
with snacks (Table 1). The intervention started in hospital and was continued for 12 months 
after discharge from the hospital.  
 
 

Table 1 Nutritional content of each intervention products. 
 
 
 
 
Oral nutritional supplement drinks 
 
 
 
Product 
Portion size  
Energy (kcal) 
Protein (g) 
 
 
 
 
Nutridrink compact (Nutricia) 
   e.g. vanilla, banana, strawberry and chocolate 
125 ml 
300 
12 
 
 
 
 
Nutridrink compact fiber (Nutricia) 
   -vanilla, strawberry and mokka  
125 ml 
300 
12 
 
 
 
 
Nutridrink (Nutricia) 
   -vanilla, strawberry, banana, and chocolate 
200 ml 
300 
12 
 
 
 
 
Nutridrink juice style (Nutricia) 
   e.g. blackcurrant, apple and orange 
200 ml 
300 
8 
 
 
 
 
Nutridrink creme (Nutricia) 
   -forest fruit and chocolate 
125 g 
200 
12 
 
 
 
 
Mean 
 
280 
11 
 
 
 
 
In-between meals snack  
 
 
 
Product 
Portion size  
Energy (kcal) 
Protein (g) 
 
 
 
 
Blueberry skyr with cream (MS Dairies) 
Skyr 140 g  
Cream 20 ml  
254 
17 
 
 
 
 
Two mini skyr with cream (MS Dairies) 
    -vanilla, strawberry and banana 
Skyr 167 g   
Cream 20 ml  
274 
16 
 
 
 
 
Rye bread (Myllan) with liver paté (Ora) and 
butter (MS Dairies) 
Rye bread 55 g 
Liver paté 40 g 
Butter 10 g 
313 
7 
 
 
 
 
Pan bread (Myllan) with ham- and egg salat 
(Sómi)  
Pan bread 47 g 
Salat 55 g  
262 
8 
 
 
 
 
Oat biscuits (Frón) with butter, cheese and glass of 
milk (MS Dairies) 
Oat biscuit 20 g 
Butter 10 g  
Cheese 20 g  
Milk 150 ml  
342 
12 
 
 
 
 
Nutbar (Himneskt) with milk (MS Dairies)   
Nutbar 40 g   
Milk 150 ml 
302 
10 
 
 
 
 
Cheesecake (MS Dairies) 
    -raspberry and chocolate 
100 g 
322 
6 
 
 
 
 
Mean 
 
286 
11 
 
 

Subjects in group 1 were offered a variety of flavours and pack sizes of ONS free of 
charge. As the hospital had a contract with Nutricia (Icepharma, Iceland) that was the brand 
used. Subjects in group 2 were provided with snacks free of charge, based on common 
Icelandic food products, e.g., Icelandic skyr which is a high protein milk product similar to 
yogurt. Patients in both groups were encouraged to consume two or more ONS or Snacks 
daily providing approximately 600 kcal/day and approximately 22 g protein/day in addition to 
regular food depending on which group they were in.(Collins, Stratton, & Elia, 2012; Ferreira, 
Brooks, White, & Goldstein, 2012) 
The selected ONS were delivered to the patient’s home or picked up at the wholesaler 
and the food packages were delivered to patient’s home or collected from the hospital, 
according to patient preference. It was assumed that each delivery of ONS and Snacks would 
last for one month and two to three weeks, respectively. A leaflet designed for this study was 
provided with pictures of different ONS or each snack and written advice regarding their use 
such as suggestions on timing of intake, choosing a lower volume (125 ml each) when 
appetite was poor (ONS) and choice of different meals (Snacks). For some items, patients had 
to portion the snacks themselves, e.g., a whole cheesecake, because the minimal available 
pack size was more than one portion.  
Verbal advice on the use of each intervention was also given to both groups, e.g., ONS 
should be used from the fridge and snacks with less expiry date should be used first.  
All patients could phone the study investigator if they needed more ONS or snacks and 
every month each patient received a call to ascertain the quantity remaining. If patients were 
admitted to hospital during the study period they received ONS or snacks according to 
randomisation during their hospital stay. 
During every follow-up appointment and during any hospital readmissions similar 
time was spent with each group. 
 
Outcomes  
Outcomes related to feasibility were percentage of eligible subjects that accepted participation 
(recruitment), percentage of included subjects that finished the 12 months intervention period 
(retention), the feasibility of undertaking functional assessment and use of ONS/snacks 
assessed by 24 hour recalls (compliance). 
The primary outcome was efficacy of the interventions assessed as weight change 
from baseline to one year from admission to the hospital. Assessment of body composition i.e. 

fat mass, fat free mass and muscle mass was conducted using a portable, multi- frequency 
(20kHz, 100kHz) bioelectrical impedance analysis (BIA) device (InBody230 Co., Ltd. 
Korea). The method has previously been validated in stable COPD patients. (Schols, 
Broekhuizen, Weling-Scheepers, & Wouters, 2005) 
The secondary outcome measures were QoL measured using the St George’s 
Respiratory Questionnaire (SGRQ). This validated questionnaire is based on 76 items used to 
calculate three component scores: symptoms, activity and impact, and a total score. A score of 
100 represents worst possible health status and a score of 0 represents best possible health 
status. (Jones, Quirk, Baveystock, & Littlejohns, 1992) A change of 4 points in the SGRQ 
total score is considered the minimum clinically relevant difference. (Jones, 2002) 
Other outcomes measures included were forced expiratory volume in one second 
(FEV1), forced vital capacity (FVC) measured by spirometry (Jaeger MS-PFT®, Care Fusion, 
San Diego, USA), (Vogelmeier et al., 2017) functional performance using several tests 
validated in COPD patients were included: six-minute walk distance (6MWD), (Singh et al., 
2014) timed up and go (TUG), (Mesquita et al., 2016) 30 second chair stand (Kato et al., 
2014) and hand-grip strength (HGS) (Puhan, Siebeling, Zoller, Muggensturm, & ter Riet, 
2013) measured by a handheld dynamometer (Jamar® Sammons Preston Rolyan, 
Boilingbrook, IL, USA) and energy- and protein intake during hospital stay and at home (two 
and four weeks after discharge). 
Total energy- and protein intake during hospital stay was estimated using a validated 
plate diagram sheet (Bjornsdottir et al., 2013; Vilhjalmsdottir, Hinriksdottir, Pordardottir, 
Porsdottir, & Gunnarsdtotir, 2013) for three days, starting on the first day of participation in 
the study and after the intervention had started.  
Energy- and protein intake at home was assessed using the 24-hour recall method, 
(Salvador Castell, Serra-Majem, & Ribas-Barba, 2015) two and four weeks after hospital 
discharge and analysed using the ICEFOOD nutritional analysis program. (Thorgeirsdottir et 
al., 2011) For full details of study assessments (see Appendix 1). 
Statistical analysis   
All statistical analyses were undertaken using IBM SPSS Statistics 24 and the level of 
significance was set at 0.05.  
Our original power calculations were based on the primary outcome of difference in 
weight gain between the groups and change in weight to one year. Due to low recruitment rate 

and lower participation rates than expected, post-hoc power calculations were performed 
based on our results.  
The Kolmogorov-Smirnov test was used to test data normality. The independent t-test was 
used to test for differences between continuous data at baseline and the Pearson's chi-squared 
test was used for categorical data. Intention-to-treat analyses were conducted where the last 
observations were carried forward and used to assess treatment efficacy. All patients with at 
least two measures (baseline and one other) were included. Repeated measures ANCOVA 
was conducted to analyse mean changes in each follow up.  
 
 
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