Trial Outcomes & Findings for A Placebo-Controlled Study of Clonidine for Fecal Incontinence. (NCT NCT00884832)

NCT ID: NCT00884832

Last Updated: 2014-03-06

Results Overview

The FICA severity scale has 4 items (frequency, type, amount of leakage, and presence of urgency) and is used to rate the severity of fecal incontinence. The parameter was computed from values in the weekly diaries. The FICA score can range from 1 to 13. Symptom severity scores of 1-6, 7-10, and 11-13 are categorized as mild, moderate, and severe, respectively. Scores were averaged over the 4 week baseline period and the 4 week treatment periods.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 44 participants
• Primary outcome timeframe: 4 weeks baseline, 4 weeks treatment
• Results posted on: 2014-03-06

Participant Flow

This study was conducted between January 2009 and April 2012.

Participant milestones

Measure	Oral Clonidine Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Overall Study STARTED	22	22
Overall Study COMPLETED	22	21
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Oral Clonidine Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

A Placebo-Controlled Study of Clonidine for Fecal Incontinence.

Baseline characteristics by cohort

Measure	Oral Clonidine n=22 Participants Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo n=22 Participants Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.	Total n=44 Participants Total of all reporting groups
Age, Continuous	58 years STANDARD_DEVIATION 10.88 • n=5 Participants	57 years STANDARD_DEVIATION 11.86 • n=7 Participants	57.38 years STANDARD_DEVIATION 11.26 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	22 Participants n=7 Participants	44 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants	22 participants n=7 Participants	44 participants n=5 Participants
Body Mass Index	30.3 kg/m^2 STANDARD_DEVIATION 1.09 • n=5 Participants	28.0 kg/m^2 STANDARD_DEVIATION 6.35 • n=7 Participants	29.14 kg/m^2 STANDARD_DEVIATION 5.81 • n=5 Participants
Hysterectomy Hysterectomy	9 participants n=5 Participants	11 participants n=7 Participants	20 participants n=5 Participants
Hysterectomy No Hysterectomy	13 participants n=5 Participants	11 participants n=7 Participants	24 participants n=5 Participants
Functional diarrhea or Diarrhea-predominant Irritable Bowel Syndrome (IBS) Subjects with diarrhea	9 participants n=5 Participants	13 participants n=7 Participants	22 participants n=5 Participants
Functional diarrhea or Diarrhea-predominant Irritable Bowel Syndrome (IBS) Subjects without diarrhea	13 participants n=5 Participants	9 participants n=7 Participants	22 participants n=5 Participants

PRIMARY outcome

Timeframe: 4 weeks baseline, 4 weeks treatment

Population: Intent to treat analysis

The FICA severity scale has 4 items (frequency, type, amount of leakage, and presence of urgency) and is used to rate the severity of fecal incontinence. The parameter was computed from values in the weekly diaries. The FICA score can range from 1 to 13. Symptom severity scores of 1-6, 7-10, and 11-13 are categorized as mild, moderate, and severe, respectively. Scores were averaged over the 4 week baseline period and the 4 week treatment periods.

Outcome measures

Measure	Oral Clonidine n=22 Participants Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo n=22 Participants Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Mean Fecal Incontinence and Constipation Assessment (FICA) Score 4 weeks baseline	8.1 units on a scale Standard Error 0.4	9.1 units on a scale Standard Error 0.3
Mean Fecal Incontinence and Constipation Assessment (FICA) Score 4 weeks treatment	6.5 units on a scale Standard Error 0.6	7.6 units on a scale Standard Error 0.5

SECONDARY outcome

Timeframe: 4 weeks baseline, 4 weeks treatment

Population: Intent to treat analysis

Values were averaged over 4 week baseline and 4 week treatment periods.

Outcome measures

Measure	Oral Clonidine n=22 Participants Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo n=22 Participants Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Mean Number of Days With Fecal Incontinence 4 weeks baseline	13 days Standard Error 1	16 days Standard Error 2
Mean Number of Days With Fecal Incontinence 4 weeks treatment	8 days Standard Error 1	11 days Standard Error 2

SECONDARY outcome

Timeframe: 4 weeks baseline, 4 weeks treatment

Population: Intent to treat analysis

Values were averaged over 4 week baseline and 4 week treatment periods.

Outcome measures

Measure	Oral Clonidine n=22 Participants Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo n=22 Participants Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Mean Number of Fecal Incontinence Episodes 4 weeks baseline	20 number of episodes Standard Error 3	31 number of episodes Standard Error 5
Mean Number of Fecal Incontinence Episodes 4 weeks treatment	12 number of episodes Standard Error 3	19 number of episodes Standard Error 4

SECONDARY outcome

Timeframe: 4 weeks baseline, 4 weeks treatment

Population: Intent to treat analysis

Values were averaged over 4 week baseline and 4 week treatment periods.

Outcome measures

Measure	Oral Clonidine n=22 Participants Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo n=22 Participants Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Mean Percentage of Bowel Movements Which Were Incontinent 4 weeks baseline	31 percentage of bowel movements Standard Error 4	40 percentage of bowel movements Standard Error 6
Mean Percentage of Bowel Movements Which Were Incontinent 4 weeks treatment	24 percentage of bowel movements Standard Error 5	27 percentage of bowel movements Standard Error 6

SECONDARY outcome

Timeframe: 4 weeks baseline, 4 weeks treatment

Population: Intent to treat analysis

The Fecal Incontinence Severity Index was used to compute the severity of fecal incontinence (FI). It is a validated 4-item scale used to assess the frequency of 4 different types of FI (gas, mucus, liquid stool, solid stool). The subject responses are weighted and summed for the 4 types of FI. Scores could range from 0 (no symptoms) to 61 (very frequent FI). Values were computed from pre- and post- treatment questionnaires.

Outcome measures

Measure	Oral Clonidine n=22 Participants Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo n=22 Participants Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Mean Severity of Fecal Incontinence 4 weeks baseline	36.2 units on a scale Standard Error 2.7	37.3 units on a scale Standard Error 2.5
Mean Severity of Fecal Incontinence 4 weeks treatment	29.3 units on a scale Standard Error 2.8	31.2 units on a scale Standard Error 2.7

SECONDARY outcome

Timeframe: 4 weeks baseline

Population: Intent to treat analysis

Scores were computed from a pre-treatment questionnaire, the Fecal Incontinence Quality of Life Scale. This scale is composed of a total of 29 items; these items form four scales: Lifestyle (10 items) Coping/Behavior (9 items), Depression/Self Perception (7 items), and Embarrassment (3 items).

Scales range from 1 to 4; with a 1 indicating a lower functional status of quality of life. Scales scores are the average (mean) response to all items in the scale (that is, add the responses to all questions in a scale together and then divide by the number of items in the scale, adjusting for missing values).

Outcome measures

Measure	Oral Clonidine n=22 Participants Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo n=22 Participants Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Impact of Fecal Incontinence on Baseline Quality of Life Coping score	1.8 units on a scale Standard Error 0.1	1.6 units on a scale Standard Error 0.1
Impact of Fecal Incontinence on Baseline Quality of Life Depression score	3.2 units on a scale Standard Error 0.2	2.9 units on a scale Standard Error 0.2
Impact of Fecal Incontinence on Baseline Quality of Life Embarrassment score	2.2 units on a scale Standard Error 0.2	2.3 units on a scale Standard Error 0.2
Impact of Fecal Incontinence on Baseline Quality of Life Lifestyle score	2.8 units on a scale Standard Error 0.2	2.3 units on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: after 4 weeks treatment

Population: Intent to treat analysis

Scores were computed from a post-treatment questionnaire, the Fecal Incontinence Quality of Life Scale. This scale is composed of a total of 29 items; these items form four scales: Lifestyle (10 items) Coping/Behavior (9 items), Depression/Self Perception (7 items), and Embarrassment (3 items).

Scales range from 1 to 4; with a 1 indicating a lower functional status of quality of life. Scales scores are the average (mean) response to all items in the scale (that is, add the responses to all questions in a scale together and then divide by the number of items in the scale, adjusting for missing values).

Outcome measures

Measure	Oral Clonidine n=22 Participants Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo n=22 Participants Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Impact of Fecal Incontinence on Post-Treatment Quality of Life Lifestyle score	3.1 units on a scale Standard Error 0.2	2.7 units on a scale Standard Error 0.2
Impact of Fecal Incontinence on Post-Treatment Quality of Life Coping score	2.3 units on a scale Standard Error 0.2	2.1 units on a scale Standard Error 0.1
Impact of Fecal Incontinence on Post-Treatment Quality of Life Depression score	3.5 units on a scale Standard Error 0.1	3.2 units on a scale Standard Error 0.2
Impact of Fecal Incontinence on Post-Treatment Quality of Life Embarrassment score	2.8 units on a scale Standard Error 0.2	2.5 units on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: 4 weeks baseline, 4 week treatment

Population: Intent to treat analysis

This parameter was determined by a 100 mm visual analog scale, with possible scores ranging from 0 = "Not satisfied at all (no relief of symptoms)" to 100 = "Completely satisfied (symptoms resolved)." The parameter was computed from weekly diaries. Scores were averaged over the 4 week baseline period and the 4 week treatment periods.

Outcome measures

Measure	Oral Clonidine n=22 Participants Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo n=22 Participants Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Satisfaction With Treatment 4 weeks baseline	22 units on a scale Standard Error 6	18 units on a scale Standard Error 4
Satisfaction With Treatment 4 weeks treatment	47 units on a scale Standard Error 6	38 units on a scale Standard Error 6

SECONDARY outcome

Timeframe: 4 weeks baseline, 4 weeks treatment

Population: Intent to treat analysis

Rectal urgency is defined as a sudden, irresistible need to have a bowel movement. Scores were averaged over the 4 week baseline period and the 4 week treatment periods.

Outcome measures

Measure	Oral Clonidine n=22 Participants Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo n=22 Participants Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Percentage of Bowel Movements Preceded by Rectal Urgency 4 weeks baseline	55 percentage of bowel movements Standard Error 4	59 percentage of bowel movements Standard Error 5
Percentage of Bowel Movements Preceded by Rectal Urgency 4 weeks treatment	46 percentage of bowel movements Standard Error 6	46 percentage of bowel movements Standard Error 6

SECONDARY outcome

Timeframe: 4 weeks baseline, 4 weeks treatment

Population: Intent to treat analysis

The percentage of bowel movements with semi-formed and loose stools was defined as those with a score of 5-7 on the Bristol stool form scale.

Outcome measures

Measure	Oral Clonidine n=22 Participants Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo n=22 Participants Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Percentage of Bowel Movements With Semi-formed and Loose Stools in Subjects With and Without Diarrhea 4 weeks baseline, subjects without diarrhea	19.4 percentage of bowel movements Standard Error 4.9	25.5 percentage of bowel movements Standard Error 6.2
Percentage of Bowel Movements With Semi-formed and Loose Stools in Subjects With and Without Diarrhea 4 weeks baseline, subjects with diarrhea	47.5 percentage of bowel movements Standard Error 8.1	51.6 percentage of bowel movements Standard Error 6.4
Percentage of Bowel Movements With Semi-formed and Loose Stools in Subjects With and Without Diarrhea 4 weeks treatment, subjects without diarrhea	14 percentage of bowel movements Standard Error 4.2	16 percentage of bowel movements Standard Error 7.2
Percentage of Bowel Movements With Semi-formed and Loose Stools in Subjects With and Without Diarrhea 4 weeks treatment, subjects with diarrhea	31.2 percentage of bowel movements Standard Error 7	49 percentage of bowel movements Standard Error 5.5

SECONDARY outcome

Timeframe: 4 weeks treatment

Population: Intent to treat analysis

The percentage of bowel movements with semi-formed and loose stools was defined as those with a score of 5-7 on the Bristol stool form scale. The "adjustment for baseline" was an analysis of covariance (ANCOVA) where the covariate was the baseline version of the endpoint.

Outcome measures

Measure	Oral Clonidine n=22 Participants Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo n=22 Participants Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Percentage of Bowel Movements With Semi-formed and Loose Stools Post-treatment Adjusted for Baseline Subjects with diarrhea	23.6 percentage of bowel movements Standard Error 4.8	38.7 percentage of bowel movements Standard Error 4.3
Percentage of Bowel Movements With Semi-formed and Loose Stools Post-treatment Adjusted for Baseline Subjects without diarrhea	25.4 percentage of bowel movements Standard Error 4.3	22.8 percentage of bowel movements Standard Error 4.8

SECONDARY outcome

Timeframe: 4 weeks baseline, 4 weeks treatment

Outcome measures

Measure	Oral Clonidine n=22 Participants Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo n=22 Participants Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Percentage of Days With Fecal Incontinence (FI) 4 weeks baseline, subjects without diarrhea	28.7 percentage of days Standard Error 5.5	37.8 percentage of days Standard Error 10.6
Percentage of Days With Fecal Incontinence (FI) 4 weeks baseline, subjects with diarrhea	35.4 percentage of days Standard Error 7.2	42.1 percentage of days Standard Error 8.1
Percentage of Days With Fecal Incontinence (FI) 4 weeks treatment, subjects without diarrhea	23.2 percentage of days Standard Error 7.1	18.7 percentage of days Standard Error 5.4
Percentage of Days With Fecal Incontinence (FI) 4 weeks treatment, subjects with diarrhea	24.3 percentage of days Standard Error 8.5	33.3 percentage of days Standard Error 9.8

SECONDARY outcome

Timeframe: 4 weeks treatment

The "adjustment for baseline" was an analysis of covariance (ANCOVA) where the covariate was the baseline version of the endpoint.

Outcome measures

Measure	Oral Clonidine n=22 Participants Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo n=22 Participants Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Percentage of Days With FI Post-treatment Adjusted for Baseline Subjects without diarrhea	42.54 percentage of days Standard Error 5.92	31.42 percentage of days Standard Error 6.97
Percentage of Days With FI Post-treatment Adjusted for Baseline Subjects with diarrhea	27.79 percentage of days Standard Error 6.97	39.51 percentage of days Standard Error 5.94

Adverse Events

Oral Clonidine

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Oral Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Oral Clonidine n=22 participants at risk Subjects randomized to Clonidine will take 0.1 mg of the medication orally twice a day for a total of 4 weeks.	Oral Placebo n=22 participants at risk Subjects randomized to the placebo group will also take 0.1 mg of matching placebo pills orally twice a day for a total of 4 weeks.
Gastrointestinal disorders Dry Mouth	72.7% 16/22 • Number of events 16	4.5% 1/22 • Number of events 1
General disorders Drowsiness	22.7% 5/22 • Number of events 5	13.6% 3/22 • Number of events 3
General disorders Lightheadedness	27.3% 6/22 • Number of events 6	9.1% 2/22 • Number of events 2
General disorders Fatigue	36.4% 8/22 • Number of events 8	22.7% 5/22 • Number of events 5

Additional Information

Dr. Adil E. Bharucha

Mayo Clinic

Phone: 507-266-9156

Email: bharucha.adil@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place