A DOUBLE-BLIND PLACEBO CONTROLLED STUDY OF CLONIDINE AND COLESEVELAM FOR FECAL INCONTINENCE (FI)

Introduction:
Fecal incontinence is associated with substantial impacts on quality of life. Prevalence estimates range from 2% to as high as 20% based on the methodology used, and is likely underreported by patients. Prior studies have demonstrated inconsistent effects of body-mass index on fecal incontinence. This study sought to further clarify the impact of modifiable measured physical indices of body mass on fecal incontinence in a nationally representative cross-sectional cohort of participants.
Methods:
This study analyzed the National Health and Nutrition Examination Survey (NHANES), an annual cross-sectional, nationally representative health survey. Surveys collected between 2005-2010 included survey components assessing bowel health. Fecal incontinence was defined by accidental bowel leakage of solid stool, liquid, or mucus at least once in the past month. Sample weight adjustment was performed to account for complex survey design. Stepwise multivariate logistic regression models were constructed to assess risk factors for fecal incontinence.
Results:
14,345 participants were identified with responses to the bowel health survey. After stepwise adjustment for covariates (including demographics, comorbidities, dietary factors, socioeconomic factors, depression scores, diarrhea, marijuana use, Figure 1), 7,530 participants were included in the final multivariate model (Figure 2). Waist circumference-height ratio was a significant predictor of fecal incontinence (OR 1.73, 95% CI 1.04-2.88, p=0.036) comparing the 4^th to the 1^st quartile of values. Quartiles of BMI, conversely, did not significantly predict fecal incontinence.
Conclusions:
Waist circumference-height ratio is a significant risk factor for fecal incontinence. While waist-circumference-height ratio predicted fecal incontinence, body-mass index did not. This suggests bowel continence depends on how body mass is distributed. Further study of the role of central deposition of body mass in neuromuscular control of bowel continence is warranted.

BACKGROUND. Some women with urge-predominant fecal incontinence (FI) have a stiffer rectum and rectal hypersensitivity. In a phase 2 study, the a₂ adrenergic agonist clonidine, which increases rectal compliance and reduces rectal sensation, did not reduce FI in all women with urge FI, but had borderline significant effects in women with diarrhea and urge FI. Up to 25% of patients with idiopathic diarrhea have bile acid malabsorption, which may respond to bile acid sequestrants. HYPOTHESES. Clonidine and colesevelam (CC) will improve fecal continence in women with urge FI. METHODS. Symptoms were recorded for 2-4 weeks before and 4 weeks during randomization to placebo or oral clonidine 0.1mg bid and colesevelam 625 mg tid in 59 women with urge-predominant FI who did not have an organic GI disorder. Bowel symptoms (daily diaries and other questionnaires), anal pressures, and rectal sensation were assessed. The last 2 wks of the baseline period and weeks 2-4 of treatment phase were analyzed. Fecal Incontinence Symptom Severity (FISS) score, fecal incontinence severity index (FISI) and FISI-QoL were computed pre- and during treatment. For the primary outcome (number of FI episodes), missing data were conservatively imputed using the average for all participants. RESULTS. At baseline, placebo and CC groups were not different (Table 1); on average patients had moderately severe FI. After the baseline phase, 3, 1 and 51 patients respectively completed 1, 2, and 4 wks of therapy; 1 eligible patient did not begin therapy and 3 patients were not eligible to receive therapy. Several measures of FI (number of episodes of FI, satisfaction with treatment) improved with placebo (Table 2). The primary outcome (≥50% reduction in FI episodes) was not different between CC (13/24 [54%]) and placebo (17/32 [53%]). Compared to placebo, CC improved the FISS but not other bowel symptoms. Among 21 and 30 patients who completed 4 wks of CC and placebo, the change (treatment – baseline) in FI episodes during therapy was directly correlated with the rectal urge sensory threshold (r_s= 0.50, P =.03) in the CC but not in the placebo group (r_s= 0.17, P =.34). CONCLUSION. In this controlled study, 53% of patients treated with placebo reported a >50% reduction in the number of FI episodes; for this outcome, effects of CC were not significant vs placebo. But, CC did improve the FISS score, which incorporates frequency, type, and amount of leakage and rectal urgency vs placebo. CC but not placebo was more effective in pts with a higher rectal sensory threshold volume for urgency, which suggests that is more likely to be effective in pts without rectal hypersensitivity. Future controlled trials should evaluate the utility of CC in patients who have documented bile acid malabsorption.