Effects of ROSE-010 on GI Transit in Constipation Predominant Irritable Bowel Syndrome (C-IBS) Patients

NCT01056107 | Completed Phase 1 Results

• 2 other identifiers: 09-005871UL1RR024150
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This trial will study the effects of an investigational (not FDA approved) medication, ROSE-010, on the movement of food through the stomach, small intestine and colon in females with constipation predominant irritable bowel syndrome (C-IBS). The study hypothesis is that ROSE-010 will delay gastric emptying of solids and enhances gastric accommodation without retarding colonic transit in female patients with C-IBS.

Conditions

Irritable Bowel Syndrome Constipation Predominant

Keywords

Constipation, Irritable Bowel Syndrome (IBS), Glucagon Like Peptide analogue

Outcome Measures

Primary Outcomes (3)

• Colonic Transit, Colonic Geometric Center at 24 Hours

  The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit, a GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.

  24 hours (Visit 3 = Day 1)

• Change Between Postprandial and Fasting Whole Gastric Volume by Technetium-99m (99mTc)-SPECT Imaging (Gastric Accommodation)

  A noninvasive SPECT method was used to measure gastric volume during fasting and 32 min after a liquid nutritional supplement meal. Subjects reported to the clinic after an overnight fast. 99mTC was giving by an intravenous injection in the forearm. The first fasting scan was obtained, and the study medication was given s.c. After 10 min, a 2nd fasting post medication scan was obtained, and the meal consumed; then two serial postprandial scans were obtained. Each scan required 9-12 min. Tomographic images of the gastric wall were obtained throughout the long axis of the stomach using a dual-head gamma camera that rotates around the body. This allows assessment of the radiolabeled circumference of the gastric wall, rather than the intragastric content. For this outcome measure, the scans for the "fasting volume" and 2 "postprandial volumes" were used. The 2 postprandial (PP) volumes were averaged. Change was calculated as (PP - Fasting = gastric accommodation).

  approximately 1 hour after 99mTC injection, approximately 30 min after liquid meal (Visit 5 = approximately 2-10 days after Visit 4)

• Half Time (t1/2) of Gastric Emptying of Solids Measured by Scintigraphy (Gastric Transit)

  Half time (t1/2) of gastric emptying (GE) of solids is the time for half of the ingested solids or liquids to leave the stomach. The scintigraphy for GE t1/2 was done on Visit 2 (Day 0 of the study), the first day of scintigraphy.

  approximately 2 hours after radiolabeled meal is ingested (Visit 2 = Day 0)

Secondary Outcomes (7)

• Gastric Residual at 2 and 4 Hours Measured by Scintigraphy

  2 hours, 4 hours (Visit 2 = Day 0)

• Colonic Geometric Center at 4 h Measured by Scintigraphy

  4 hours (Visit 2 = Day 0)

• Colonic Filling at 6 h Measured by Scintigraphy

  6 hours (Visit 2 = Day 0)

• Ascending Colon Emptying Half-time (AC t1/2) Measured by Scintigraphy

  48 hours (Visit 4 = Day 2)

• Colonic Transit, Colonic Geometric Center at 48 h Measured by Scintigraphy, as Compared to Placebo.

  48 hours (Visit 4 = Day 2)

Study Arms (4)

ROSE-010 30 mcg

EXPERIMENTAL

A glucagon-like peptide-1 (GLP-1) analogue. Subjects received a ROSE-010 30 mcg subcutaneous injection daily for 3 consecutive days and on 1 day 2-10 days later.

Drug: ROSE-010

ROSE-010 100 mcg

EXPERIMENTAL

A glucagon-like peptide-1 (GLP-1) analogue. Subjects received a ROSE-010 100 mcg subcutaneous injection daily for 3 consecutive days and on 1 day 2-10 days later.

Drug: ROSE-010

ROSE-010 300 mcg

EXPERIMENTAL

A glucagon-like peptide-1 (GLP-1) analogue. A glucagon-like peptide-1 (GLP-1) analogue. Subjects received a ROSE-010 300 mcg subcutaneous injection daily for 3 consecutive days and on 1 day 2-10 days later.

Drug: ROSE-010

Placebo

PLACEBO COMPARATOR

Subjects received a matching placebo subcutaneous injection daily for 3 consecutive days and on 1 day 2-10 days later.

Drug: Placebo

Interventions

ROSE-010 DRUG

The study medication was used in 30 mcg, 100 mcg, and 300 mcg subcutaneous injections daily, depending upon study arm.

Also known as: Glucagon-like peptide-1 (GLP-1) analogue

ROSE-010 100 mcg; ROSE-010 30 mcg; ROSE-010 300 mcg

Placebo DRUG

Placebo subcutaneous injection daily

Also known as: Glucagon-like peptide-1 (GLP-1) analogue

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female aged 18-65 years old inclusive.
• A previous diagnosis of IBS according to Rome III criteria to include those patients who have had recurrent abdominal pain or discomfort for the at least the six months prior to diagnosis and currently at least three days per month in the last three months associated with two or more of the following:
• improvement with defecation
• onset associated with a change in the frequency of stool
• onset associated with a change in form (appearance) of stool.
• Constipation predominant type IBS as defined by one or more of the following:
• fewer than three spontaneous complete bowel movements per week
• hard or lumpy stools more than 25% of the time
• straining during a bowel movement more than 25% of the time.
• A normal rectal exam result on file within the past two years or performed at screen 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 by more than one centimeter on straining and last, spasm, tenderness or paradoxical contraction of the puborectalis muscles.
• Females of child bearing potential (those who have not experienced a bilateral tubal ligation, hysterectomy or menopause) must use an acceptable method of contraception during the study. Acceptable methods are surgical sterilization, hormonal methods such as oral contraceptives, Norplant and Depo-Provera, double barrier method such as a condom and spermicide, and an intrauterine device (IUD). Abstinent females may participate if they agree to use the double barrier method should they become sexually active during the study.
• Able to provide written informed consent prior to any study procedures being performed.

You may not qualify if:

• Female patients who are pregnant or breast-feeding.
• Structural or metabolic diseases/conditions that affect the gastrointestinal system, or functional gastrointestinal disorders other than C-IBS.
• Unable to withdraw medications 48 hours prior to the study: any medication that alters GI transit including but not limited to laxatives, magnesium or aluminum-containing antacids, prokinetics, erythromycin, narcotics, anticholinergics, tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors (SNRIs); analgesic drugs including opiates, nonsteroidal anti-inflammatory drugs (NSAIDs), and COX 2 inhibitors (Note: Tylenol is permitted), GABAergic agents and benzodiazepines. Note: All other concomitant medications will be reviewed on a case by case basis by the study physicians.
• Clinical evidence (including but not limited to a clinically significant abnormal physical exam, ECG or laboratory result 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 PI. If the laboratory test result remains abnormal and clinically significant, the patient will be referred to a primary care physician for further evaluation.
• Patients who are considered by the Investigator to be alcoholics not in remission or known substance abusers.
• Patients who have participated in another clinical study within the past 30 days.

Sponsors & Collaborators

• Mayo Clinic: lead
• Rose Pharma A/S: collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Camilleri M, Vazquez-Roque M, Iturrino J, Boldingh A, Burton D, McKinzie S, Wong BS, Rao AS, Kenny E, Mansson M, Zinsmeister AR. Effect of a glucagon-like peptide 1 analog, ROSE-010, on GI motor functions in female patients with constipation-predominant irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2012 Jul;303(1):G120-8. doi: 10.1152/ajpgi.00076.2012. Epub 2012 Apr 19.

  PMID: 22517769 RESULT

MeSH Terms

Conditions

Constipation; Irritable Bowel Syndrome; Ichthyosis Bullosa of Siemens

Interventions

glucagon-like peptide (7-37), valyl(10)-; Glucagon-Like Peptide 1

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Ichthyosis; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Dr. Michael Camilleri
• Organization: Mayo Clinic

camilleri.michael@mayo.edu

507-266-2305

Study Officials

• Michael Camilleri, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 22, 2010
• First Posted: January 26, 2010
• Study Start: January 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: May 31, 2013
• Results First Posted: May 31, 2013

Record last verified: 2013-04

Locations

US (1)