Madisch 2007.
| Methods | Randomized, double‐blind, placebo‐controlled trial performed at multiple German centres. Duration of study was 6 weeks. Study had potential crossover for the non‐responders in the placebo group | |
| Participants | Patients (n = 31) aged 18‐80 years with clinically and histologically confirmed collagenous colitis ("at least five liquid or soft stools per day on average per week, and a complete colonoscopy performed within the last 4 weeks before randomization") Histological diagnosis made with colonoscopy with biopsy: main criteria was collagen band > 10 um thick Other analyzed criteria included inflammation of lamina propria (semi‐quantitative definition) and degeneration of surface epithelium (qualitative definition) Patients were excluded if they had other endoscopically or histologically verified causes for diarrhea, infectious diarrhea, pregnancy or lactation, previous colonic surgery, or known intolerance to Boswellia serrata extract. Patients who had received therapy within 4 weeks of randomization were also excluded if therapies included budesonide, salicylates, steroids, prokinetics, antibiotics, ketoconazole, or non‐steroidal anti‐inflammatt ory drugs |
|
| Interventions |
Boswellia serrata extract (three 400 mg/day capsules) versus placebo for 6 weeks Cross‐over therapy offered to non‐responders after 6 weeks, open‐labelled BSE 400 mg po t.i.d |
|
| Outcomes | Primary endpoint was clinical remission after 6 weeks (stool frequency of < 3 per day) stool frequency of less than 3 per day Secondary endpoints were histological changes and quality of life Histological (via colonoscopy with biopsy): improvement in baseline parameters Quality of life: assessed with SF‐36 surveys at the beginning and at the end of 6 weeks of therapy "Stool frequency and consistency, intake of study medication, adverse events, and any intake of allowed concomitant medication were assessed by standardized questionnaire" "Patients who did not respond to treatment after 6 weeks were individually unblinded. If they were in the active treatment group, they were judged as treatment failure. If they were in the placebo group, crossover therapy with open‐labelled BSE 400 mg, given orally three times daily was offered" |
|
| Notes | During the first three weeks of treatment loperamide was allowed as rescue medication. "Patients were allowed to use butylscopolamine in case of abdominal pain" Steroids, anti‐inflammatory drugs, immunosuppressives, antibiotics, prokinetics and bismuth compounds were not allowed during the study |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomization was via a central computer generated randomization list in groups of four patients |
| Allocation concealment (selection bias) | Low risk | Quote: "central computer‐generated randomization list" |
| Blinding (performance bias and detection bias) All outcomes | Low risk | Quote: "double‐blind" Quote: "Physicians, patients, and pathologist were blinded to the treatment group. Study medication was provided in identical‐ looking white boxes labelled with consecutive numbers corresponding to the randomization list. In addition, the placebo containers were prepared from the inside to mimic the typical scent of incense to prevent unblinding by the typical odour of BSE." |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 5/31 patients discontinued (4 patients, reasons described) the trial or were lost to follow‐up (1 patient). All 31 patients were included in the intention‐to‐treat analysis, 26 patients were included in the per‐protocol analysis |
| Selective reporting (reporting bias) | Low risk | All outcomes were reported |
| Other bias | Low risk | Study appeared to be free of other forms of bias |