Colorectal CancerPhase 1NCT01950403
Linaclotide Acetate in Preventing Colorectal Cancer in Healthy Volunteers
A Phase 1 study testing linaclotide acetate, pharmacological study and laboratory biomarker analysis in people with Colorectal Cancer and Healthy, no Evidence of Disease, run by Mayo Clinic at 1 site in United States.
Trial summary
This randomized phase I trial studies the side effects and best dose of linaclotide acetate in preventing colorectal cancer in healthy volunteers. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of linaclotide acetate may prevent colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Colorectal Cancer, Healthy, no Evidence of Disease
- What is being tested?
- linaclotide acetate, pharmacological study and laboratory biomarker analysis
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2013to 22 Feb 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- PRE-REGISTRATION INCLUSION CRITERIA
- Ability to understand and willingness to sign a written informed consent document and follow study procedures
- Willingness to abstain from grapefruit juice, alcohol, and concomitant medications during study
- Willingness to employ adequate contraception for men and women of childbearing potential; acceptable methods include double barrier methods, intrauterine device (IUD), postmenopausal status documented by serum follicle-stimulating hormone (FSH), and/or documentation of surgical sterilization
- Body mass index < 35 kg/m^2
- Willingness to provide blood and tissue specimens for research purposes
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- REGISTRATION INCLUSION CRITERIA
- Participants must have normal organ function and have normal laboratory findings without clinically significant findings
- Satisfactory anesthesia and intestinal preparation, with no findings of advanced adenoma, chronic inflammation, or cancer
Who cannot join
- PRE-REGISTRATION EXCLUSION CRITERIA
- Previous personal history of advanced adenomas (>= 1 cm in maximal diameter, >= 3 in total number, villous morphology, or high-grade dysplasia) or colorectal cancer
- Family history of polyposis syndrome (e.g., familial adenomatous polyposis [FAP], hereditary non-polyposis colorectal cancer [HNPCC]) or colorectal cancer (first degree relatives younger than 60 years old)
- History of gastroparesis
- History of surgery involving the luminal gastrointestinal (GI) tract, including bariatric surgery
- History of celiac disease
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- Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- Irritable bowel syndrome, chronic constipation, functional bowel disorders, or colonic motility disorder
- Any malignancy within 3 years of baseline; participants with a history of basal cell or squamous cell skin cancer may be enrolled at the discretion of the investigator
- Participants may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to linaclotide
- History of difficulty with colonoscopy or abnormal colorectal anatomy
- Uncontrolled current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant or lactating women
- Use of laxatives more than 3 times per week
- Intestinal motility agents, histamine-2 inverse agonists (H-2 blockers), or proton pump inhibitors
- Current use of >= 5 cigarettes/day
- Current use of >= 3 alcoholic drinks/day
- Use anti-platelet agents within two weeks of anticipated colonoscopy
- Use of anti-coagulants within two weeks of anticipated colonoscopy
- History of bleeding/coagulation problems
- Prior intolerance of or contraindications for the use of sedation or anesthetic agents, which would prevent the safe use of sedation for colonoscopy; this includes allergies to eggs and soy products
- Any medical condition judged by the investigator to constitute a risk to safe participation
- REGISTRATION EXCLUSION CRITERIA
- Colonoscopic finding requiring clinical intervention
- Use of any illicit or illegal substances detected by urinary drug screen
- Inadequate pre-intervention bowel preparation, as determined by the study physician
Trial locations and contacts
1 site in 1 country.
United States1 site
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
Official title: Phase I, Randomized, Placebo-Controlled Trial of Linaclotide to Demonstrate Colorectal Bioactivity in Healthy Volunteers
This randomized phase I trial studies the side effects and best dose of linaclotide acetate in preventing colorectal cancer in healthy volunteers. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of linaclotide acetate may prevent colorectal cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the pharmacodynamic effect (PD) of linaclotide (linaclotide acetate) (single daily dose x 7 days, stage I cohort dose= 0.870 mg/day) on cyclic guanosine monophosphate (cGMP) levels, based on biopsy samples obtained pre- and post-intervention from the rectum, until an effect is documented.
SECONDARY OBJECTIVES:
- To confirm the safety and tolerability of linaclotide. II. To assess the pharmacodynamic effect of linaclotide on cGMP levels, analyzed sequentially from the transverse colon to the cecum, if no cGMP effect was observed in the rectum for the primary endpoint.
III. To compare the change in the cGMP levels from baseline to day 7 between all the assigned doses of linaclotide (including placebo), analyzed sequentially from the rectum, transverse colon, and cecum.
IV. If the study proceeds to stage II, the pharmacodynamic effect of linaclotide on cGMP levels will be assessed from day 6 rectal biopsies (un-prepped).
TERTIARY OBJECTIVES:
- To assess the pharmacodynamic effect of linaclotide on an additional pathway-specific biomarkers relevant to guanylate cyclase C (GCC) signaling (i.e., vasodilator-stimulated phosphoprotein [VASP] phosphorylation) and a marker of general proliferation (Ki67 expression), based on intestinal mucosa biopsy samples obtained by colonoscopy pre- and post-exposure at the anatomical location (rectum, transverse colon, or cecum) in which cGMP is elevated following linaclotide exposure.
OUTLINE: This is a dose-escalation study. Participants are randomized to 1 of 2 treatment arms.
ARM I: Participants receive linaclotide acetate orally (PO) once daily (QD) on days 1-7.
ARM II: Participants receive placebo PO QD on days 1-7.
After completion of treatment, participants are followed up for 21-51 days.
- Conditions
- Colorectal Cancer, Healthy, no Evidence of Disease
- Being tested
- linaclotide acetate, placebo, pharmacological study, laboratory biomarker analysis
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
linaclotide acetateDrug
Also called Linzess, MD-1100 Acetate, MM-416775
Given PO
placeboOther
Also called PLCB
Given PO
Also called pharmacological studies
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (linaclotide acetate) | Experimental | Participants receive linaclotide acetate PO QD on days 1-7. Receives: Drug: linaclotide acetate; Other: pharmacological study; Other: laboratory biomarker analysis |
| Arm II (placebo) | Placebo comparator | Participants receive placebo PO QD on days 1-7. Receives: Other: placebo; Other: pharmacological study; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose of linaclotide acetate that produces a 60% response rate for cGMP levels in rectal tissue by radioimmunoassay (RIA)
The pharmacological effect is measured by the arithmetic difference in mean cGMP levels before and after 7 days of linaclotide acetate in biopsies from the colonoscopy. The mean cGMP value will be calculated based on 2 biopsies from the rectum assessed at each time point. The PD response is measured by the difference in mean cGMP levels after 7 days.
Measured: Baseline to 7 days
Secondary outcomes (4)
Incidence of adverse events associated with linaclotide acetate assessed using the Common Terminology Criteria for Adverse Events version 4.0
Summary statistics, frequency tables, and non-parametric tests will be used to describe the distributions of adverse events.
Measured: Up to 51 days
PD effect of linaclotide acetate on cGMP levels from the transverse colon to the cecum
Measured: Up to 7 days
Change in cGMP levels between all assigned doses, analyzed sequentially from the rectum, transverse colon, and cecum
Summary statistics and nonparametric tests will be used to compare the change in the cGMP levels between the different dose levels of linaclotide acetate and placebo.
Measured: Baseline to 7 days
PD effect on cGMP levels (Stage II)
Changes in cGMP levels from baseline to day 6 will also be assessed using summary statistics and nonparametric tests.
Measured: Up to 6 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2013 (estimated)
- Study startSep 2013
- Primary completion28 Apr 2016
- Study completion22 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Paul Limburg, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01950403
- Sponsor's protocol ID
- MAY2012-00-01
- Other IDs
- NCI-2013-01788, HHSN2512012000042I, 13-829, MAY2012-00-01, MAY2012-00-01, N01CN00042
- Status last verified
- May 2018
- First submitted
- 23 Sep 2013
- Last updated
- 9 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Randomized, Placebo-Controlled Trial of Linaclotide to Demonstrate Colorectal Bioactivity in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01950403
- Acronym / sponsor ID
- MAY2012-00-01
- Conditions
- Colorectal Cancer, Healthy, no Evidence of Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2013 (actual)
- Primary completion
- 28 Apr 2016 (actual)
- Study completion
- 22 Feb 2018 (actual)
- First posted
- 25 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase I trial studies the side effects and best dose of linaclotide acetate in preventing colorectal cancer in healthy volunteers. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of linaclotide acetate may prevent colorectal cancer.
Detailed description
PRIMARY OBJECTIVES:
- To assess the pharmacodynamic effect (PD) of linaclotide (linaclotide acetate) (single daily dose x 7 days, stage I cohort dose= 0.870 mg/day) on cyclic guanosine monophosphate (cGMP) levels, based on biopsy samples obtained pre- and post-intervention from the rectum, until an effect is documented.
SECONDARY OBJECTIVES:
- To confirm the safety and tolerability of linaclotide. II. To assess the pharmacodynamic effect of linaclotide on cGMP levels, analyzed sequentially from the transverse colon to the cecum, if no cGMP effect was observed in the rectum for the primary endpoint.
III. To compare the change in the cGMP levels from baseline to day 7 between all the assigned doses of linaclotide (including placebo), analyzed sequentially from the rectum, transverse colon, and cecum.
IV. If the study proceeds to stage II, the pharmacodynamic effect of linaclotide on cGMP levels will be assessed from day 6 rectal biopsies (un-prepped).
TERTIARY OBJECTIVES:
- To assess the pharmacodynamic effect of linaclotide on an additional pathway-specific biomarkers relevant to guanylate cyclase C (GCC) signaling (i.e., vasodilator-stimulated phosphoprotein [VASP] phosphorylation) and a marker of general proliferation (Ki67 expression), based on intestinal mucosa biopsy samples obtained by colonoscopy pre- and post-exposure at the anatomical location (rectum, transverse colon, or cecum) in which cGMP is elevated following linaclotide exposure.
OUTLINE: This is a dose-escalation study. Participants are randomized to 1 of 2 treatment arms.
ARM I: Participants receive linaclotide acetate orally (PO) once daily (QD) on days 1-7.
ARM II: Participants receive placebo PO QD on days 1-7.
After completion of treatment, participants are followed up for 21-51 days.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (linaclotide acetate) | Experimental | Drug: linaclotide acetate, Other: pharmacological study, Other: laboratory biomarker analysisParticipants receive linaclotide acetate PO QD on days 1-7. |
| Arm II (placebo) | Placebo comparator | Other: placebo, Other: pharmacological study, Other: laboratory biomarker analysisParticipants receive placebo PO QD on days 1-7. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- PRE-REGISTRATION INCLUSION CRITERIA
- Ability to understand and willingness to sign a written informed consent document and follow study procedures
- Willingness to abstain from grapefruit juice, alcohol, and concomitant medications during study
- Willingness to employ adequate contraception for men and women of childbearing potential; acceptable methods include double barrier methods, intrauterine device (IUD), postmenopausal status documented by serum follicle-stimulating hormone (FSH), and/or documentation of surgical sterilization
- Body mass index < 35 kg/m^2
Key exclusion criteria (27 listed)
- PRE-REGISTRATION EXCLUSION CRITERIA
- Previous personal history of advanced adenomas (>= 1 cm in maximal diameter, >= 3 in total number, villous morphology, or high-grade dysplasia) or colorectal cancer
- Family history of polyposis syndrome (e.g., familial adenomatous polyposis [FAP], hereditary non-polyposis colorectal cancer [HNPCC]) or colorectal cancer (first degree relatives younger than 60 years old)
- History of gastroparesis
- History of surgery involving the luminal gastrointestinal (GI) tract, including bariatric surgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| linaclotide acetateAlso: Linzess, MD-1100 Acetate, MM-416775Given PO | Drug | Arm I (linaclotide acetate) |
| placeboAlso: PLCBGiven PO | Other | Arm II (placebo) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Arm I (linaclotide acetate), Arm II (placebo) |
| laboratory biomarker analysisCorrelative studies | Other | Arm I (linaclotide acetate), Arm II (placebo) |
Primary outcome
Dose of linaclotide acetate that produces a 60% response rate for cGMP levels in rectal tissue by radioimmunoassay (RIA)
Time frame: Baseline to 7 days
The pharmacological effect is measured by the arithmetic difference in mean cGMP levels before and after 7 days of linaclotide acetate in biopsies from the colonoscopy. The mean cGMP value will be calculated based on 2 biopsies from the rectum assessed at each time point. The PD response is measured by the difference in mean cGMP levels after 7 days.
4 secondary outcomes
Incidence of adverse events associated with linaclotide acetate assessed using the Common Terminology Criteria for Adverse Events version 4.0
Time frame: Up to 51 days
PD effect of linaclotide acetate on cGMP levels from the transverse colon to the cecum
Time frame: Up to 7 days
Change in cGMP levels between all assigned doses, analyzed sequentially from the rectum, transverse colon, and cecum
Time frame: Baseline to 7 days
PD effect on cGMP levels (Stage II)
Time frame: Up to 6 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Limburg principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing linaclotide acetate, pharmacological study and laboratory biomarker analysis in people with Colorectal Cancer and Healthy, no Evidence of Disease, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose of linaclotide acetate that produces a 60% response rate for cGMP levels in rectal tissue by radioimmunoassay (RIA) (time frame: Baseline to 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2024.