title: Colesevelam for the treatment of bile acid malabsorption-associated diarrhea in patients with Crohn's disease: a randomized, double-blind, placebo-controlled study.
abstract: OBJECTIVE
  Bile acid malabsorption (BAM)-associated diarrhea is an important clinical issue in patients with Crohn's disease (CD). We analyzed the efficacy and safety of the bile acid sequestrant colesevelam for treatment of BAM-associated diarrhea in CD patients in a randomized, double-blind, placebo-controlled study.
  
  
  METHODS
  The primary endpoint was the proportion of patients with >30% reduction of liquid stools/day from baseline to termination visit at week 4. Secondary endpoints were reduction of the number of liquid stools/day, improvement of stool consistency and quality of life.
  
  
  RESULTS
  26 patients were analyzed in the intention-to-treat (ITT) analysis. The primary endpoint was reached by 10 patients (69.7%) in the colesevelam group compared to 3 patients (27.3%) in the placebo group (risk difference RD=.394, 95%CI:[-0.012; 0.706]; P=.0566). In the per-protocol analysis (n=22), the risk difference was statistically significant (RD=.470, 95%CI:[0.018; 0.788], P(H0: RD=0)=0.0364; 95% CI:[1.3;54.7]). Regarding secondary endpoints, in the ITT population colesevelam-treated patients had a significant reduction of liquid stools/day at week 4 (median 5.0 to 2.0; P=0.01), while patients treated with placebo had no significant reduction (median 4.0 to 3.0; P=0.42). Significantly more patients in the colesevelam group had improvement of stool consistency of at least one level in the Bristol stool chart, as compared to the placebo group (P=0.003).
  
  
  CONCLUSIONS
  We found significant differences in favor for colesevelam treatment compared to placebo treatment for CD patients with BAM regarding the reduction of the number of liquid stools/day and stool consistency. ClinicalTrials.gov number: NCT01203254.
authors: Department of Medicine II, University Hospital Munich-Grosshadern, Ludwig-Maximilians-University Munich, Germany. Electronic address: florian.beigel@med.uni-muenchen.de.
authors: Florian
authors: F
authors: Beigel
authors: Internal Practice, Leipzig, Germany.
authors: Niels
authors: N
authors: Teich
authors: Internal Practice, Hamburg, Germany.
authors: Stefanie
authors: S
authors: Howaldt
authors: Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
authors: Frank
authors: F
authors: Lammert
authors: Department for Gastroenterology, Infectious Diseases and Rheumatology Charité-Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors: Jochen
authors: J
authors: Maul
authors: Department of Medicine II, University Hospital Munich-Grosshadern, Ludwig-Maximilians-University Munich, Germany.
authors: Simone
authors: S
authors: Breiteneicher
authors: Department of Medicine II, University Hospital Munich-Grosshadern, Ludwig-Maximilians-University Munich, Germany; Department of Medicine II, Krankenhaus Barmherzige Brüder, Munich, Germany.
authors: Christian
authors: C
authors: Rust
authors: Department of Medicine II, University Hospital Munich-Grosshadern, Ludwig-Maximilians-University Munich, Germany.
authors: Burkhard
authors: B
authors: Göke
authors: Department of Medicine II, University Hospital Munich-Grosshadern, Ludwig-Maximilians-University Munich, Germany.
authors: Stephan
authors: S
authors: Brand
authors: Department of Medicine II, University Hospital Munich-Grosshadern, Ludwig-Maximilians-University Munich, Germany; Isarmedizin Zentrum, Munich, Germany.
authors: Thomas
authors: T
authors: Ochsenkühn
mesh_terms: D000328:Adult; D000368:Aged; D000499:Allylamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001647:Bile Acids and Salts / Q000378:metabolism*; D002783:Cholestenones / Q000097:blood; D000069472:Colesevelam Hydrochloride; D003424:Crohn Disease / Q000150:complications* / Q000601:surgery; D003967:Diarrhea / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D005243:Feces; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008286:Malabsorption Syndromes / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D002783:Cholestenones; D000499:Allylamine; D000069472:Colesevelam Hydrochloride
keywords: Bile acid malabsorption; Colesevelam; Crohn's disease; Diarrhea