Familial Adenomatous PolyposisPhase 2NCT00641147
Curcumin in Treating Patients With Familial Adenomatous Polyposis
A Phase 2 study testing Curcumin and Laboratory Biomarker Analysis in people with Familial Adenomatous Polyposis, run by National Cancer Institute (NCI) at 2 sites in 2 countries.
Trial summary
This randomized phase II trial studies curcumin in treating patients with familial adenomatous polyposis. Curcumin may prevent colorectal cancer in patients with a history of rectal polyps or colorectal neoplasia. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Familial Adenomatous Polyposis
- What is being tested?
- Curcumin and Laboratory Biomarker Analysis
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Oct 2010to 30 Nov 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with familial adenomatous polyposis who have undergone subtotal colectomy with ileorectal anastomosis, total colectomy with ileo-anal pull through (reservoir), and patients with intact colons with 5 or more adenomas in the rectum-sigmoid or reservoir
- Patients with familial adenomatous polyposis (FAP) and duodenal adenomatous polyposis without current lower tract adenomatous polyposis i.e. status/post (s/p) ileostomy
Who cannot join
- Female patients of childbearing age not on effective birth control
- Pregnant women
- White blood cell count (WBC) < 3500/ml
- Platelet count < 100,000/ml
- Blood urea nitrogen (BUN) > 25mg%
- Creatinine > 1.5mg%
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- Patients unable to stop non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, curcumin, tumeric, calcium, vitamin D, green tea, or polyphenol E supplements for the duration of the trial
- Malignancy other than nonmelanoma skin cancer
- Active bacterial infection
- Patients with symptoms of active gastroesophageal reflux disease (GERD) (symptomatic despite medication or current erosive esophagitis on endoscopy)
- Patients with a history of peptic ulcer disease
- Patients on warfarin or plavix
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
About this study
Official title: Curcumin for Treatment of Intestinal Adenomas in Familial Adenomatous Polyposis (FAP)
This randomized phase II trial studies curcumin in treating patients with familial adenomatous polyposis. Curcumin may prevent colorectal cancer in patients with a history of rectal polyps or colorectal neoplasia.
Read the detailed description
Specific Aims:
- To determine in a randomized, double-blinded, placebo-controlled study the tolerability and effectiveness of curcumin to regress intestinal adenomas by measuring duodenal and colorectal/ileal polyp number, and polyp size in familial adenomatous polyposis patients with intact colons, ileorectal anastomosis surgery, or ileo-anal pullthrough (reservoir) surgery.
II. To measure markers of cell proliferation including colorectal mucosal levels of ornithine decarboxylase (ODC), polyamines, mucosal deoxyribonucleic acid (DNA) methylation, proliferative index (Ki67 antiproliferative cell nuclear antibody), apoptosis index, vascular density, mucosal prostaglandin, leukotriene levels, and activation of the nuclear factor kappa B (NFKB), and v-akt murine thymoma viral oncogene homolog 1 (Akt) survival pathways.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive curcumin orally (PO) twice daily (BID) for 12 months.
Arm II: Patients receive placebo PO BID for 12 months.
After completion of study treatment, patients are followed up at 4 months.
- Conditions
- Familial Adenomatous Polyposis
- Being tested
- Curcumin, Laboratory Biomarker Analysis, Placebo
- Medical subject headings
- Adenomatous Polyposis Coli
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CurcuminDrug
Also called C.I. 75300, C.I. Natural Yellow 3, Diferuloylmethane, Turmeric Yellow
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
PlaceboOther
Also called placebo therapy, sham therapy
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (curcumin) | Experimental | Patients receive curcumin PO BID for 12 months. Laboratory Biomarker Analysis Receives: Drug: Curcumin; Other: Laboratory Biomarker Analysis |
| Arm II (placebo) | Placebo comparator | Patients receive placebo PO BID for 12 months. Laboratory Biomarker Analysis Receives: Other: Laboratory Biomarker Analysis; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Polyp Number
Average number of polyps in the placebo arm at the end of the study is compared to the average in the curcumin arm
Measured: Up to 12 months
Secondary outcomes (11)
Mean Polyp Size in mm
Mean size of the 5 largest polyps
Measured: Up to 12 months
Number of Participants With a Decrease in Polyp Burden at 12 Months
The polyp burden as evaluated by video tape review. Polyp burden at 12 months compared to time 0 for each participant and counting participants with decrease in polyp burden at 12 months.
Measured: 12 months
Number of Participants With Grade >=2 Adverse Events
Events were graded as follows:
Grade 0= no adverse event or within normal limits; Grade 1= mild adverse event (causing no limitations of usual activity); Grade 2= moderate adverse event (causing some limitation of activity); Grade 3= severe adverse event (severe and undesirable; causing inability to carry out usual activities; Grade 4= life threatening or disabling adverse event; Grade 5= fatal adverse event.
Measured: Up to 12 months
Medication Compliance
Medication compliance of the participant= number of capsules taken divided by the number of capsules prescribed as determined by pill count and described as a percentage per participant. Then the compliance of each participant in the assigned group (curcumin or placebo) was averaged together to obtain the medication compliance rate of that group.
Measured: Up to 12 months
Change in Ornithine Decarboxylase (ODC) Activity Levels
Change in ODC mean activity levels (expressed as nmol of activity/mg of mucosal tissue/hr) at 8 months compared to baseline (time 0)
Measured: Baseline and 8 months
Change in Total Polyamines Levels
Polyamine mean level changes (expressed as pg/mg protein) at month 8-baseline
Measured: Baseline and 8 months
Change in Micro RNA 124-U6 (miR124-U6)
Change in MicroRNA mean activity level at 8 months compared to baseline (time 0)
Measured: Baseline and 8 months
Change in Spermidine/Spermine N-1 Acetyl Transferase (SSAT)
Change in SSAT mean activity level at 8 months compared to baseline (time 0)
Measured: Baseline and 8 months
Change in Spermine Oxidase (SMOX)
Change in SMOX mean activity level at 8 months compared to baseline (time 0)
Measured: Baseline and 8months
Change in Ki-67 Anti-proliferative Cell Nuclear Antibody Index Levels
Change in cellular proliferation rate was measured by assessment of Ki-67 anti-proliferative cell nuclear antibody index levels at 8 months
Measured: Baseline up to 8 months
Change in Apoptosis Index Levels
Change in apoptosis index levels at 8 months by assessing cleaved Caspase-3 measurement
Measured: 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2008 (estimated)
- Study startOct 2010
- Primary completionNov 2016
- Study completion30 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Familial Adenomatous PolyposisStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Francis Giardiello, Principal investigator, Johns Hopkins University/Sidney Kimmel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00641147
- Sponsor's protocol ID
- NCI-2013-00536
- Other IDs
- NCI-2013-00536, CDR0000592794, NA_00011821, 1R01CA134620, R01CA134620, P30CA006973
- Status last verified
- Sep 2017
- First submitted
- 17 Mar 2008
- Last updated
- 29 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Cruz-Correa M, Hylind LM, Marrero JH, Zahurak ML, Murray-Stewart T, Casero RA Jr, Montgomery EA, Iacobuzio-Donahue C, Brosens LA, Offerhaus GJ, Umar A, Rodriguez LM, Giardiello FM. Efficacy and Safety of Curcumin in Treatment of Intestinal Adenomas in Patients With Familial Adenomatous Polyposis. Gastroenterology. 2018 Sep;155(3):668-673. doi: 10.1053/j.gastro.2018.05.031. Epub 2018 May 23.
PubMed 29802852
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Curcumin for Treatment of Intestinal Adenomas in Familial Adenomatous Polyposis (FAP)
- ClinicalTrials.gov ID
- NCT00641147
- Acronym / sponsor ID
- NCI-2013-00536
- Conditions
- Familial Adenomatous Polyposis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2010
- Primary completion
- Nov 2016 (actual)
- Study completion
- 30 Nov 2016 (actual)
- First posted
- 24 Mar 2008 (estimated)
- Results
- Posted 29 Sep 2017
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 II trial studies curcumin in treating patients with familial adenomatous polyposis. Curcumin may prevent colorectal cancer in patients with a history of rectal polyps or colorectal neoplasia.
Detailed description
Specific Aims:
- To determine in a randomized, double-blinded, placebo-controlled study the tolerability and effectiveness of curcumin to regress intestinal adenomas by measuring duodenal and colorectal/ileal polyp number, and polyp size in familial adenomatous polyposis patients with intact colons, ileorectal anastomosis surgery, or ileo-anal pullthrough (reservoir) surgery.
II. To measure markers of cell proliferation including colorectal mucosal levels of ornithine decarboxylase (ODC), polyamines, mucosal deoxyribonucleic acid (DNA) methylation, proliferative index (Ki67 antiproliferative cell nuclear antibody), apoptosis index, vascular density, mucosal prostaglandin, leukotriene levels, and activation of the nuclear factor kappa B (NFKB), and v-akt murine thymoma viral oncogene homolog 1 (Akt) survival pathways.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive curcumin orally (PO) twice daily (BID) for 12 months.
Arm II: Patients receive placebo PO BID for 12 months.
After completion of study treatment, patients are followed up at 4 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (curcumin) | Experimental | Drug: Curcumin, Other: Laboratory Biomarker AnalysisPatients receive curcumin PO BID for 12 months. Laboratory Biomarker Analysis |
| Arm II (placebo) | Placebo comparator | Other: Laboratory Biomarker Analysis, Other: PlaceboPatients receive placebo PO BID for 12 months. Laboratory Biomarker Analysis |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with familial adenomatous polyposis who have undergone subtotal colectomy with ileorectal anastomosis, total colectomy with ileo-anal pull through (reservoir), and patients with intact colons with 5 or more adenomas in the rectum-sigmoid or reservoir
- Patients with familial adenomatous polyposis (FAP) and duodenal adenomatous polyposis without current lower tract adenomatous polyposis i.e. status/post (s/p) ileostomy
Key exclusion criteria (12 listed)
- Female patients of childbearing age not on effective birth control
- Pregnant women
- White blood cell count (WBC) < 3500/ml
- Platelet count < 100,000/ml
- Blood urea nitrogen (BUN) > 25mg%
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 |
|---|---|---|
| CurcuminAlso: C.I. 75300, C.I. Natural Yellow 3, Diferuloylmethane, Turmeric YellowGiven PO | Drug | Arm I (curcumin) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (curcumin), Arm II (placebo) |
| PlaceboAlso: placebo therapy, sham therapyGiven PO | Other | Arm II (placebo) |
Primary outcome
Polyp Number
Time frame: Up to 12 months
Average number of polyps in the placebo arm at the end of the study is compared to the average in the curcumin arm
11 secondary outcomes
Mean Polyp Size in mm
Time frame: Up to 12 months
Number of Participants With a Decrease in Polyp Burden at 12 Months
Time frame: 12 months
Number of Participants With Grade >=2 Adverse Events
Time frame: Up to 12 months
Medication Compliance
Time frame: Up to 12 months
Change in Ornithine Decarboxylase (ODC) Activity Levels
Time frame: Baseline and 8 months
Change in Total Polyamines Levels
Time frame: Baseline and 8 months
Change in Micro RNA 124-U6 (miR124-U6)
Time frame: Baseline and 8 months
Change in Spermidine/Spermine N-1 Acetyl Transferase (SSAT)
Time frame: Baseline and 8 months
Change in Spermine Oxidase (SMOX)
Time frame: Baseline and 8months
Change in Ki-67 Anti-proliferative Cell Nuclear Antibody Index Levels
Time frame: Baseline up to 8 months
Change in Apoptosis Index Levels
Time frame: 8 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29802852Cruz-Correa M, Hylind LM, Marrero JH, Zahurak ML, Murray-Stewart T, Casero RA Jr, Montgomery EA, Iacobuzio-Donahue C, Brosens LA, Offerhaus GJ, Umar A, Rodriguez LM, Giardiello FM. Efficacy and Safety of Curcumin in Treatment of Intestinal Adenomas in Patients With Familial Adenomatous Polyposis. Gastroenterology. 2018 Sep;155(3):668-673. doi: 10.1053/j.gastro.2018.05.031. Epub 2018 May 23.
- Individual participant dataSharing planned: No
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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.
Francis Giardiello principal investigator
Johns Hopkins University/Sidney Kimmel Cancer Center
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Curcumin and Laboratory Biomarker Analysis in people with Familial Adenomatous Polyposis, run by National Cancer Institute (NCI) at 2 sites in 2 countries.
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 2 inclusion and 12 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 29 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Puerto Rico. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Polyp Number (time frame: Up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00641147, which also lists 1 linked publication.
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 29 Sep 2017.