An Effectiveness and Safety Study of Chinese Herbal Medicine for Functional Constipation

• Responder of Complete Spontaneous Bowel Movement (CSBM) [ Time Frame: End of treatment (wk10) ] [ Designated as safety issue: No ]
  Patients with a mean increase of ≧1 complete spontaneous bowel movement(CSBM)/wk compared with the baseline(wk1-2) will be defined as responders. CSBM referred to the feeling that defecation led to complete passage of stool rather than partial or incomplete evacuation without the use of any laxative or enema within 24 hours.
  
  

• Responder of Complete Spontaneous Bowel Movement (CSBM) [ Time Frame: End of follow up (wk18) ] [ Designated as safety issue: No ]

  Participants with a mean increase of complete spontaneous bowel movement (CSBM)>=1 movement per week compared with the last 14 days of the run-in period were defined as responders.

  CSBM referred to the feeling that defecation led to complete passage of stool rather than partial or incomplete evacuation without the use of any laxative or enema within 24 hours.

  
  
• Bowel Movement [ Time Frame: Baseline(Wk1&2), Within treatment(Wk3-10) & Within follow-up(Wk11-18) ] [ Designated as safety issue: No ]
  
• Complete Spontaneous Bowel Movement (CSBM) [ Time Frame: Baseline(Wk1&2), Within treatment(Wk3-10), Within follow-up(Wk11-18) ] [ Designated as safety issue: No ]
  
• Changes on Individual Symptom Scores [ Time Frame: Baseline(Wk2), Within treatment(Wk6), End of treatment(Wk10) & End of follow-up(Wk18) ] [ Designated as safety issue: No ]
  It was a 7-point ordinal scale from 0=not at all to 6=very severe.
  
  
• Global Symptoms Improvement [ Time Frame: Wk 6, 10 & wk 18 ] [ Designated as safety issue: No ]
  Participants were asked to rate their impression of change in constipation by comparing with their baseline (Wk2) at the visits during the treatment (Wk6), end of treatment (Wk10) and end of follow-up (Wk18) with scores from 0 to 6 represented markedly worse or better respectively. The response categories were collapsed to simply "improved" for score 4 to 6, "same" for score 3 or "worse" for score 0 to 2.
  
  
• Success of Blinding [ Time Frame: End of follow-up (Wk18) ] [ Designated as safety issue: No ]
  The success of blinding was evaluated for both investigator and patients as to whether MZRW or placebo had been taken.
  
  
• Blood Urea Level [ Time Frame: Pre-treatment (Wk2) & Post-treatment (Wk10) ] [ Designated as safety issue: Yes ]
  
• Blood Creatinine Level [ Time Frame: Pre-treatment (Wk2) & Post-treatment (Wk10) ] [ Designated as safety issue: Yes ]
  
• Serum Glutamic Pyruvic Transaminase(SGPT) Level [ Time Frame: Pre-treatment (Wk2) & Post-treatment (Wk10) ] [ Designated as safety issue: Yes ]
  
• Serum Glutamic Oxaloacetic Transaminase (SGOT) [ Time Frame: Pre-treatment (Wk2) & Post-treatment (Wk10) ] [ Designated as safety issue: Yes ]
  

Constipation is a common gastrointestinal complaint in clinical practice, which affects in estimated 12%-19% of American, 14% of Asian, and up to 27% of the population depending on demographic factor, sampling, and definition. With the unsatisfactory response to current symptomatic treatments, many patients seek help from traditional Chinese medicine (TCM), mostly by taking Chinese herbal medicine (CHM).

According to the TCM theory, constipation can be broadly divided into two types, excessive and deficient, based on the underlying aetiology. The former is characterized by the presence of Heat or pathological accumulation of Qi. Heat causes constipation by drying the Intestines and the stool. Patients present with hard, dry, pellet like stool, red complexion, dry mouth or halitosis, red tongue with a dry yellow coat, and slippery and rapid pulse. Qi stagnation causes constipation by disrupting the normal movement and descent of Stomach and Intestinal Qi. Patients present difficulty in passing stools, feelings of incomplete evacuation, abdominal distension or pain, frequent belching and flatulence, tongue with thin coat and wiry pulse. The latter, deficient constipation, is delineated as the dryness from insufficient fluid lubrication in the form of blood or lack of propulsion power from the deficiency of Qi or Yang. Besides, the treatment approaches vary from syndrome to syndrome.

The formula of MaZiRenWan (MZRW) composed of six Chinese herbs is firstly recorded in a TCM classic, Discussion of Cold-induced Disorders (Shang Han Lun), and it has been commonly used for constipation in excessive pattern throughout Asia since the Han Dynasty (A.D. 200). By combining the actions of these herbs, MZRW can moisten the Intestines, drain heat, promote the movement of Qi and unblock the bowel. Although previous studies show that MZRW has purgative and laxative effects and may be useful for functional constipation (FC), there are significant methodological weaknesses. Furthermore, the dose of CHM intervention being investigated from the first randomized controlled trial (RCT) published in 1983 is always based on the practitioner's experience, TCM literatures, or experts' comments, but not the results from stringent clinical trials, such as dose determination study. Therefore, the evidence produced will be attenuated or even misleading if improper dose is taken.

In the present study, the efficacy and safety of MZRW in optimal dosage were justified by comparing with placebo under strict clinical trial design.