The challenges of control groups, placebos and blinding in clinical trials of dietary interventions

High-quality placebo-controlled evidence for food, nutrient or dietary advice interventions is vital for verifying the role of diet in optimising health or for the management of disease. This could be argued to be especially important where the benefits of dietary intervention are coupled with potential risks such as compromising nutrient intake, particularly in the case of exclusion diets. The objective of the present paper is to explore the challenges associated with clinical trials in dietary research, review the types of controls used and present the advantages and disadvantages of each, including issues regarding placebos and blinding. Placebo-controlled trials in nutrient interventions are relatively straightforward, as in general placebos can be easily produced. However, the challenges associated with conducting placebo-controlled food interventions and dietary advice interventions are protean, and this has led to a paucity of placebo-controlled food and dietary advice trials compared with drug trials. This review appraises the types of controls used in dietary intervention trials and provides recommendations and nine essential criteria for the design and development of sham diets for use in studies evaluating the effect of dietary advice, along with practical guidance regarding their evaluation. The rationale for these criteria predominantly relate to avoiding altering the outcome of interest in those delivered the sham intervention in these types of studies, while not compromising blinding.</jats:p

A multicentre study of nutrition risk assessment in adult patients with inflammatory bowel disease attending outpatient clinics

Background: Overnutrition and undernutrition can affect patients with inflammatory bowel disease (IBD). Although all IBD outpatients should be screened for nutrition risk, screening is not routinely performed, potentially leading to reduced identification and treatment. This study aimed to estimate the prevalence of nutrition risk in adult IBD outpatients and the proportion of cases who discussed diet and/or nutrition during their routine clinical appointment. Methods: Adults with IBD attending outpatient clinics at four hospitals in Greece and in UK were recruited. Demographic and anthropometric data were collected using face-to-face patient interviews and clinical records. Patients were classified as high (i.e. BMI &lt;18.5kg/m2 or 18.5-54 20kg/m2 and weight loss &gt;5%), moderate (i.e. BMI 20-25 kg/m2 and weight loss &gt;5%) or low risk of undernutrition and high risk of obesity (i.e. BMI 25-30% and weight gain &gt;5%). The proportion of patients who discussed diet and/or nutrition during their clinical appointment was calculated. Results: In total, 390 IBD patients participated. Sixteen (4%) patients were underweight, 113 (29%) were overweight and 71 (18%) were obese. Twenty-one (5%) patients were at high risk of undernutrition; of these four (19%) were under dietetic care. Of those at high risk of undernutrition, 11 (52%) had discussed diet and/or nutrition during their routine clinical appointment. Fifty-six (14%) patients had gained more than 5% weight since their last recorded/reported weight and 19 (5%) were at high risk of obesity. Conclusions: Few patients were identified to be at high risk of undernutrition and less than a fifth of these were under dietetic care. Overnutrition is a growing problem in IBD with almost half of adult patients being overweight or obese. Diet and/or nutrition were not routinely discussed in this group of IBD outpatients

A rapid, simple questionnaire to assess gastrointestinal symptoms after oral ferrous sulphate supplementation

BACKGROUND: Oral iron supplementation is often associated with rapid onset of gastrointestinal side-effects. The aim of this study was to develop and trial a short, simple questionnaire to capture these early side-effects and to determine which symptoms are more discriminating. METHODS: The study was a double-blind placebo-controlled randomized parallel trial with one week treatment followed by one week wash-out. Subjects were randomized into two treatment groups (n = 10/group) to receive either ferrous sulphate (200 mg capsules containing 65 mg of iron) or placebo, both to be taken at mealtimes twice daily during the treatment period. Subjects completed the questionnaires daily for 14 days. The questionnaire included gastrointestinal symptoms commonly reported to be associated with the oral intake of ferrous iron salts (i.e. nausea, vomiting, heartburn, abdominal pain, diarrhoea, and constipation). RESULTS: Seventy five per cent of participants reporting the presence of one or more symptoms in the first week of the study were in the ferrous sulphate group. In the second week of the study (i.e. wash-out), 67% of the participants reporting one or more symptom(s) were in the ferrous sulphate group. In the first week of the study (treatment) the number of symptoms reported by participants in the ferrous sulphate group (mean ± SEM = 6.7 ± 1.7) was significantly higher than that for participants in the placebo group (1.2 ± 0.5) (p = 0.01). In the second week of the study (wash-out) the number of symptoms reported by participants in the ferrous sulphate group (4.6 ± 2.0) appeared higher than for participants in the placebo group (1.0 ± 0.7) although this did not reach significance (p = 0.12). Events for which the gastrointestinal symptom questionnaire was most discriminatory between ferrous sulphate and placebo groups were: heartburn, abdominal pain and the presence of black stools (all p ≤ 0.03). CONCLUSIONS: A tool for the detection of commonly-occurring side effects should not require large study numbers to be effective. With just 10 subjects per group (iron or placebo), this simple questionnaire measures gastrointestinal side-effects associated with oral iron (ferrous sulphate) supplementation, and would be appropriate for use in intervention studies or clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02146053 (21/05/2014)