Design
A double-blind randomised placebo cross-over study in which participants rated symptoms daily for six months in baseline, placebo, and experimental conditions. This study was approved by our university ethics committee and was in accordance with the code of conduct for psychologists (ethical principles for conducting research with human participants) produced by the British Psychological Society. The research was conducted only when written consent was received from the participant, and their G.P. had provided written confirmation of their diagnosis, and confirmation of no other co-existing conditions.
Participants
Thirty seven people with a diagnosis of Irritable Bowel Syndrome took part in the study. The inclusion criteria were that participants should be aged 18 – 65, should have been diagnosed as having IBS by a qualified medical practitioner, and should have diarrhoea as a main symptom. The exclusion criteria were any other co-existing illnesses, and non-confirmation of the diagnosis by G.P. The participant flow is shown below (see Figure 1).
Thirty-seven participants completed the trial, during which they completed daily symptom diaries for four weeks (baseline) following by either the experimental condition (eight weeks) or the placebo condition (eight weeks). There was a four week washout period between conditions. The mucosal cell turn-over for the whole tract is approximately six days, with the majority of other cells in the body are also replaced over 30 days. For this reason a 30 day washout was selected. Although some of the participants rated some symptoms as not particularly bothersome over the baseline condition no person was excluded by us.
IBS symptoms
The symptoms of interest were: abdominal pain, diarrhoea, urgency to have a bowel movement, incomplete evacuation after a bowel movement, flatulence, bloating, and constipation. Participants rated symptoms every day on a scale of 1 ("no discomfort at all today") to 7 ("very severe discomfort today"). Reliability for these symptoms has been previously established [17].
Participants were given a pack containing a month's supply of daily diaries in which to record their symptoms. The next month's supply were sent to the participants once the previous completed pack had been returned.
Neutroceutical product
Participants took one 500 mg capsule three times a day with meals – in the experimental condition these contained the neutroceutical product IntestAidIB which consists of the following active substances: nucleotides & RNA (concentrated extracts of Saccharomyces cerevisae), hydroxypropyl methycellulose, FOS (fructo-olligosaccharides), Methionine, Glutamine, Inositol, Lysine, Pantothenic acid (Vitamin B5 as Calcium d-pantothenate), Sodium citrate, Riboflavin (Vitamin B2), Vanillin, Folic acid, and Biotin. Flow agents are magnesium stearate and silicic acid. The capsules are carbohydrate based. RNA and the specific, purified nucleotides are the natural extracts of yeast. There are no yeast cells carried over from the extraction process into the product. The daily diaries contained space where participants confirmed that they had taken each capsule, and at what time of day.
Procedure
Recruitment was by a variety of sources. Notices asking for people with diagnosed IBS interested in taking part in a trial for a neutroceutical product were sent to people with IBS who had previously expressed an interest in IBS-related research; a request was included in one issue of Gut Reaction (a quarterly journal sent to people with IBS by The IBS Network, a British self-help organisation), and notices were placed in doctors' surgeries and libraries. Such a recruitment strategy was considered necessary, as strict inclusion and exclusion criteria, plus the burden of completing daily diaries for six months meant recruitment might be difficult. We wished to have a mixed group of people with IBS, representative of the general population of people with IBS. Recruiting from tertiary centres does not allow generalisation to the wider population of people with this condition.
Participants were invited to respond to these recruitment methods by telephone or e-mail. During this initial contact, the researcher ensured that potential participants met the inclusion criteria. Eligible individuals were then given full information relating to the study. They were advised at this stage of their right to withdraw their participation and/or any data already provided, at any time, without giving any notice or reason to the research team.
Participants were then asked to provide contact details for their GP, and a consent form was sent by post to the participant for them to complete and return, as well as a pack providing further information about the trial and the supplement. Their GP was also sent a letter at this point, summarising the trial and requesting confirmation of diagnosis. Upon receipt of the confirmation of diagnosis and participant consent forms, participants were randomised to each of the conditions.
Initially participants were sent their first symptom diary pack, which contained detailed instructions on how to complete the diary as well as the first diary itself. The diary required participants to rate the severity of their symptoms (see above) and to specify the times at which they had taken each of their three capsules; to name any medications which they were prescribed, had purchased (including price) and had actually taken (including time taken) that day; and to note any visits to health professionals made that day (including who they visited, reason for visit and advice given).
Participants were contacted by telephone or e-mail a week after this first pack was sent out (week 1), to confirm that they understood how to complete the questionnaires and the diary. Participants were sent their first set of capsules (a "set" comprised four sealed tubs) – all tubs were marked "nutritional supplement, contents 42 capsules (500 mg), two weeks supply", but with A or B clearly marked both on the label and on the cap) one week before they were to need them (week 3), with a letter stating the date on which they should begin taking the capsules. They were contacted by telephone or e-mail a few days after this date (week 5) to ensure that they were taking the capsules at the right dosage (one capsules three times a day, preferably with meals), that they were completing the symptom diary with the required information (time capsules taken, any missed capsules noted), and that they were aware of how to contact the research team if they had concerns about any effect which the capsules may have upon them.
Following this, participants were sent a symptom diary pack every month, their second set of capsules for week 17, a set of questionnaires (described below) at week 13 and week 25. All documentation and capsules were sent one week before they were required to ensure that they arrived in good time. Every letter sent to the participants included contact details for the research team and urged participants to telephone or e-mail with any questions or worries, at any stage of the trial. Participants were sent questionnaire packs at baseline, washout, and end of trial.
Every participant forgot to take at least one capsule across the duration of the trial, but this was usually one capsule only on any given day. There were two exceptions – one participant took capsules erratically over the last six weeks of the experimental condition and after the first five weeks of the placebo condition. This participant had a change of personal circumstances during this time (she underwent a hysterectomy). The other participant took no capsules for 5 days in the last week of the experimental condition as she went away and forgot to take the capsules with her.
Psychological measures
Measures were taken at the beginning of the baseline period, the end of the experimental condition and the end of the placebo condition.
Depression was measured by the CES-D [18] and anxiety was measured by the Stait-Trait Anxiety inventory [19]; a specific measure of health anxiety was provided by the Health Anxiety Questionnaire [20]. General health and happiness were measured by the total of the GHQ-60 [21] and the Affect Balance Scale [22]. The extent to which IBS intrudes into various aspects of everyday life was measured by the 13-item Illness Intrusiveness Rating Scale [23].