Effect of TU-100 on Rectal Compliance, Rectal Sensation and Small Bowel and Colonic Transit in Females With Constipation

This study has been completed.
Sponsor:
Collaborator:
Cato Research
Information provided by (Responsible Party):
Tsumura USA
ClinicalTrials.gov Identifier:
NCT01139216
First received: June 3, 2010
Last updated: January 8, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to assess the dose-related effects of TU-100, a botanical agent that modulates gastrointestinal nerves, on rectal compliance, rectal sensation thresholds and small bowel and colonic transit in female patients with functional constipation as compared to placebo.


Condition Intervention Phase
Functional Constipation
Gastric Emptying
Whole Gut Transit
Small Bowel Transit
Colonic Transit
Rectal Compliance
Rectal Sensation
Drug: Daikenchuto (TU-100)
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of DAIKENCHUTO (TU-100), a Gastrointestinal Nerve Modulator, on Rectal Compliance, Rectal Sensation and Small Bowel and Colonic Transit in Female Patients With Functional Constipation

Resource links provided by NLM:


Further study details as provided by Tsumura USA:

Primary Outcome Measures:
  • Colonic geometric center at 24 hours measured by scintigraphy [ Time Frame: Up to 48 hours ] [ Designated as safety issue: No ]
  • T1/2 of ascending colon emptying as measured by scintigraphy [ Time Frame: Up to 48 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Colonic geometric center at 4 hours and 48 hours [ Time Frame: Up to 48 hours ] [ Designated as safety issue: No ]
  • Colonic filling at 6 hours [ Time Frame: Up to 48 hours ] [ Designated as safety issue: No ]
  • t1/2 of gastric emptying of solid [ Time Frame: Up to 48 hours ] [ Designated as safety issue: No ]
  • Rectal Compliance Pr1/2 [ Time Frame: Up to 3 hours ] [ Designated as safety issue: No ]
  • Rectal sensation thresholds (gas, urgency to defecate, and pain) [ Time Frame: Up to 3 hours ] [ Designated as safety issue: No ]
  • Anal sphincter pressure at rest [ Time Frame: Up to 3 hours ] [ Designated as safety issue: No ]
  • Anal sphincter pressure during squeeze [ Time Frame: Up to 3 hours ] [ Designated as safety issue: No ]
  • Recto-anal pressure difference during straining to simulate defecation [ Time Frame: Up to 3 hours ] [ Designated as safety issue: No ]
  • Stool frequency [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Stool consistency [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • PAC-QOL (Patient Assessment of Constipation Quality of Life) score [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: August 2010
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Daikenchuto (TU-100) 7.5g/day
Daikenchuto (TU-100) 2.5g TID (7.5g/day)
Drug: Daikenchuto (TU-100)
Subjects will receive 2.5g TID (7.5g/day) of TU-100. Dosage form is granule. Subject will take a daily dose divided 3 times per day for 4 weeks.
Experimental: Daikenchuto (TU-100) 15g/day
Daikenchuto (TU-100) 5g TID (15g/day)
Drug: Daikenchuto (TU-100)
Subjects will receive 5g TID (15g/day) of TU-100. Dosage form is granule. Subject will take a daily dose divided 3 times per day for 4 weeks.
Placebo Comparator: Placebo
Placebo TID
Drug: Placebo
Subjects will receive daily dose of TU-100 placebo. Dosage form is granule. Subject will take a daily dose divided 3 times per day for 4 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Meet Rome III criteria for functional constipation
  2. Willing and able to provide written informed consent
  3. Females, not pregnant or not breast-feeding

    • Females of childbearing potential must use an acceptable form of contraception during the study and for 30 days after the last dose. Acceptable methods include surgical sterilization, hormonal contraceptives (such as oral contraceptives, Depo-Provera, Nuva Ring, condoms used with a spermicide, an IUD or abstinence.
    • Females are not considered to be of childbearing potential if they are postmenopausal for at least two years or have been surgically sterilized.
  4. Ages 18 to 65 years old inclusive
  5. A body mass index (BMI) between 18 and 40 kg/m2 inclusive
  6. A negative urine drug screen at Visit 1
  7. Normal or not clinically significant laboratory results as reviewed by the study physicians
  8. A normal rectal exam result on file within the past 2 years or performed at Visit 1 in order to exclude the possibility of an evacuation disorder. Examination must exclude findings suggestive of an evacuation disorder such as high sphincter tone at rest, failure of perineal descent and spasm, tenderness or paradoxical contraction of the puborectalis muscles.
  9. Do not have sufficient criteria for irritable bowel syndrome (IBS)

Exclusion Criteria:

  1. Structural or metabolic diseases/conditions that affect the gastrointestinal system or functional gastrointestinal disorders other than constipation.
  2. Taking any medication that in the opinion of the principal investigator has a potential to alter GI transit. This includes but is not limited to osmotic or stimulant laxatives, magnesium or aluminum-containing antacids, prokinetics, erythromycin, narcotics, anticholinergics, selective norepinephrine reuptake inhibitors (SNRIs), opiates, GABAergic agents and benzodiazepines.

    • Note: Tricyclic antidepressants are permissible at doses equal to or less than 25 mg daily; selective serotonin reuptake inhibitor (SSRI) antidepressants are permissible at low, stable doses. Analgesics such as Tylenol, ibuprofen, naproxen and aspirin are permissible. All medications shall be reviewed by the principal investigator on a case by case basis.
    • Rescue medications: Rescue medications shall be reviewed and approved as necessary for exacerbation of constipation as the study medication treatment period is lengthy, about 28 days total. The patient will contact the study staff to request review and approval of the use of a rescue medication by the principal investigator. The use of the rescue medication will be documented by the patient in the bowel pattern diary. Rescue medications are not allowed within 7 days of the abbreviated baseline or the full transit scintigraphy to ensure data integrity.
  3. Clinical evidence, including but not limited to a clinically significant abnormal physical exam or laboratory test result or a past event documented in the past medical record, or current clinically significant abnormal physical exam or laboratory test result that could indicate significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurological, psychiatric or other diseases that interfere with the objectives of the study. If a laboratory test result is abnormal and clinically significant, it may be repeated once at the discretion of the principal investigator. If the laboratory test result remains abnormal and clinically significant, the patient will be discontinued from the study and referred to a primary care physician for evaluation.
  4. Patients who are considered to be alcoholics not in remission or known substance abusers.
  5. Patients who have participated in another clinical study in the past 30 days.
  6. Patients who have a history of allergic reactions to egg, ginseng, ginger or Sichuan pepper
  7. Patients who are clinically lactose intolerant
  8. Patients must agree to avoid alcohol during the days of Visits 5, 6 and 7 to avoid corrupting the data from the anorectal manometry and rectal barostat tests.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01139216

Locations
United States, Minnesota
Mayo Clinic, Rochester Methodist CRU
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Tsumura USA
Cato Research
Investigators
Principal Investigator: Michael Camilleri, MD Mayo Clinic
  More Information

No publications provided by Tsumura USA

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tsumura USA
ClinicalTrials.gov Identifier: NCT01139216     History of Changes
Other Study ID Numbers: TU100CPT2
Study First Received: June 3, 2010
Last Updated: January 8, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Tsumura USA:
Digestive system diseases
Gastrointestinal diseases
Intestinal diseases
Colonic inertia

Additional relevant MeSH terms:
Constipation
Signs and Symptoms, Digestive
Signs and Symptoms

ClinicalTrials.gov processed this record on April 15, 2014