- Click here for explanation of classification scheme.

The purpose of this study was to compare the severity, frequency, and incidence of diarrhea experienced by patients randomized to take or not take Metamucil while receiving a course of radical pelvic radiation.

• Patients with prostate or gynecologic cancer
• Undergoing radiotherapy to the pelvis of at least 4000 cGy in 20 fractions

• History of gastrointestinal [GI] disease
• History of regular use of laxatives or anti-diarrheal medications
• Tumor of the GI tract
  • Excluded to measure the effect of radiation and not the effect of cancer

Recruitment: 

• Consecutive patients with prostate or gynecologic cancer within 3 days of starting radiotherapy
• All patients were from the two site locations of the Ottowa Regional Cancer Center

 Design:

• A table of random numbers was used to assign patients to one of two groups:
  • Group 1 -- take Metamucil
  • Group 2 -- do not take Metamucil
• A different researcher at each site location met with the patients
• All patients were given a baseline assessment, diet teaching, and, if appropriate, instruction in the use of Metamucil
  • Patients were instructed in filling out diary
  • All patients received "Nutritional Guidelines to Help Control Diarrhea" booklet (Clinical Nutrition/Nutrition Services 1993)
    • This booklet was used as the basis for dietary teaching in order to ensure consistency between the researchers
    • The booklet recommends a low fiber diet, and encourages patients to avoid fat, caffeine, and alcohol
    • If part of Group 1, patient was instructed in use of Metamucil
    • Dosage during study is not specifically mentioned; however, in the "Clinical Implications" section of the study, the study authors state that the usual dose used at their institution is 1 tsp Metamucil each morning, plus 1-2 extra glasses of water above usual fluid intake per day
      • If necessary, dosage is increased to 1 tsp Metamucil twice a day
• All patients were asked to complete a diary from Day 1 of recruitment until follow-up appointment, approximately 28 days post-treatment
  • Diary recorded:
    • Number of bowel movements per day
    • Consistency of stools
    • Amount of anti-diarrhea medication taken
    • If appropriate, daily doses of metamucil
  • Compliance with filling out diary was monitored weekly during the treatment period
• Data was assessed using the Murphy Diarrhea Scale (MDS)
  • The MDS was developed by the study's first author to assess and quantify data recorded in diaries
  • Accounts for frequency and texture of stools, and use of anti-diarrheal medication
  • Assigns days-with-diarrhea a numerical score
  • MDS not yet validated but is based on the pre-existing Chary and Thomson scale, and on the National Cancer Institute of Canada, Clinical Trials Group, Expanded Toxicity Criteria

Blinding used

Researchers were not blinded to subjects' group assignment.

Intervention

• Use of Metamucil
  • Metamucil is defined as, "primarily psyllium, a dietary fibre derived from the seed of the plant 'Phantago ovatu'
  • Dosage during study is not specifically mentioned; however, in the "Clinical Implications" section of the study, the study authors state that the usual dose used at their institution is 1 tsp Metamucil each morning, plus 1-2 extra glasses of water above usual fluid intake per day
    • If necessary, dosage is increased to 1 tsp Metamucil twice a day

Statistical Analysis

• The Murphy Diarrhea Scale was used to synthesize the data collected in the pilot study
• The SAS, 1989, statistical package was used to analyze the scores generated by the MDS
  • Primary analysis method was ANOVA using the F-test
  • Significance level was p= 0.05
  • Differences in gender and site location were included in the statistical model
• MDS scores, use of anti-diarrheal medications, incidence, time of onset, duration, and severity of radiation-induced diarrhea [RID] were analyzed

 

 

Timing of Measurements

• 84 patients were recruited over a period of 18 months
• Compliance with diaries was assessed weekly during treatment period

 Dependent Variables

• Variable 1: Murphy Diarrhea Scale [MDS] mean severity score
  • Measures days-with-diarrhea
    • A day-with-diarrhea is defined as any day with one of the following criteria:
      • Four to six bowel movements more than normal
      • One or more watery bowel movements
      • Two to three loose or poorly formed bowel movements more than normal
      • Use of anti-diarrhea medication
    • MDS severity scale
      • Mild: <11% days-with-diarrhea
        • Score: 1
      • Moderate: 11-20% days-with-diarrhea
        • Score: 2
      • Severe: >20% days-with-diarrhea
        • Score: 3 
• Variable 2: Incidence of diarrhea
  • Measured from diary records
• Variable 3: Mean time to onset of diarrhea
  • Measured from diary records
• Variable 4: Mean duration in days
  • Measured from diary records
• Variable 5: Mean % days took anti-diarrhea medication
  • Measured from diary records

Independent Variables

• Presence of prostate or gynecologic cancer
• Radiotherapy to the pelvis of at least 4000 cGy in 20 fractions

 Control Variables

• Control group (No Metamucil)
• Identical dietary instruction for both groups

 

 

Initial N:

• N = 84 (72 males, 12 females)

Attrition (final N):

• N = 60 (51 males, 9 females)
  • Group 1 =30 (25 males, 5 females)
  • Group 2 = 30 (26 males, 4 females)
• Data from 24 subjects was excluded from analysis due to:
  • Voluntary withdrawal (n=1)
  • Inaccurate diary entries (n=6)
  • Incomplete diary entries (n=2)
  • Failure to return diaries (n=13)
  • Using Metamucil while in the non-Metamucil group (n=2)
• Data was not analyzed on an intent-to-treat basis

Age: 

• Group 1
  • Males: 63.7 (50-79)
  • Females: 56.3 (46-76)
• Group 2
  • Males: 66.7 (54-75)
  • Females: 64.7 (50-69)

Ethnicity:  Not mentioned; however, all patients were seen at two Canadian cancer treatment centers

Other relevant demographics: 

• Mean weight in kg:
  • Group 1
    • Males: 83.6 (61-156)
    • Females: 70.0 (67-75)
  • Group 2
    • Males: 83.1 (62-110)
    • Females: 68.6 (52-88)

Anthropometrics

• There were no significant differences between groups for mean age, age range, weight, or average dose of radiation

Location:

• Two site locations of the Ottowa Regional Cancer Center

 

Differences between Metamucil and non-Metamucil groups: 

Variables	Group 1: Metamucil group	Group 2: Non-Metamucil group	Statistical Significance of Group Difference
Murphy Diarrhea Scale mean severity score	1.80	2.33	p = 0.030**
Incidence of diarrhea	60%	83%	p = 0.049**
Mean time to onset (days)	13.9	14.1	p = 0.895
Mean duration (days)	41.5	38.5	p = 0.905
Mean % days took anti-diarrhea medication	6.70	15.10	p = 0.062*

 **statistically significant

*not statistically significant, but shows a trend

Differences between Metamucil and non-Metamucil groups excluding use of anti-diarrheal medication in definition of day-with-diarrhea

Variables	Metamucil group	Non-Metamucil group	Statistical significance of group difference
Murphy Diarrhea Scale mean severity score	1.70	2.10	p = 0.078*
Incidence of diarrhea	57%	77%	p = 0.107*
Mean time to onset (days)	14.9	16.8	p = 0.500
Mean duration (days)	42.9	42.7	p = 0.980

*not significant but a trend

Other Findings

• The use of Metamucil was associated with a reduction in the incidence and severity of RID, as well as a decrease in the use of anti-diarrheal medication
• Metamucil was well-tolerated by patients, with no complaints of GI side effects or inability to take Metamucil
  • Authors contrast with use of low-fat diet and cholestryramine to control RID; in one study 9 of 17 patients complained of nausea and cramping
• No patient required interruption of radiation treatments
  • Authors contrast with use of very low fat, low fiber diet and elemental supplements to control RID; in one study 2 of 52 patients had their treatments interrupted due to diarrhea
• Metamucil is low-cost and well-tolerated; it appears to have minimal side effects
• Metamucil appears to absorb excess liquid present due to radiation, and helps form stools

 

The results of this study support the effectiveness of Metamucil in reducing the incidence and severity of RID.

The authors list several study limitations:

• The study was a pilot study, and thus, limited in scope
• The MDS has not been validated
• The definition of "day-with-diarrhea" included "use of anti-diarrheal medication"; this may be a study limitation
  • When analysis excluded "use of anti-diarrheal medication", the same trends for incidence and severity occurred without statistical significance
  • Data were not collected on the type or dose of anti-diarrheal medications used
• The period of data collection should have been extended from the first day of radiation to follow-up at 28 days post-treatment to one week before radiation and six-eight weeks post-treatment
  • Several patients showed evidence of RID beyond the diary period

The authors urged further study of the role of Metamucil in controlling RID.

The dose of Metamucil used at the study centers was one teaspoon each morning with 1-2 glasses of water beyond usual intake.  If necessary, Metamucil was increased to 1 teaspoon twice daily.

Industry:	Proctor & Gamble Corporation Other:
University/Hospital:	Ottawa Hospital, Ottawa Regional Cancer Centre, Princess Margaret Hospital (Ontario)

• Well-designed, well-controlled pilot study
• Good discussion of study limitations
• Study focuses on an outcome that is of high concern to patients receiving radiation therapy
• Heavy reliance on patient-reported data; however, compliance was monitored weekly
• High study drop-out rate
• Results may have been biased since data were not analyzed on an intent-to-treat basis
• Researchers were not blinded to group assignment
• Although use of anti-diarrheal medications was measured, type and dosage of anti-diarrheal medications were not measured
• High proportion of males to females in each group; however, numbers of males and females were consistent between groups
• Proctor and Gamble corporation, manufacturers of Metamucil, provided partial funding for this study through a research grant