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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2013-00536 | Other Identifier | NCI | |
| CDR0000592794 | Other Identifier | Clinical Trial Reporting Program | |
| NA_00011821 | Other Identifier | Johns Hopkins University IRB | |
| 1R01CA134620 | U.S. NIH Grant/Contract | View source | |
| R01CA134620 | U.S. NIH Grant/Contract | View source | |
| P30CA006973 | U.S. NIH Grant/Contract | View source |
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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.
Specific Aims:
I. 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I (curcumin) | Experimental | Patients receive curcumin PO BID for 12 months. Laboratory Biomarker Analysis |
|
| Arm II (placebo) | Placebo Comparator | Patients receive placebo PO BID for 12 months. Laboratory Biomarker Analysis |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Curcumin | Drug | Given PO |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Polyp Size in mm | Mean size of the 5 largest polyps | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Mucosal DNA Methylation Levels. | Baseline to up to 12 months | |
| Change in Mucosal Leukotriene Levels. | Baseline to up to 12 months. | |
| Change in Mucosal Prostaglandin Levels. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Francis Giardiello | Johns Hopkins University/Sidney Kimmel Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | 21287 | United States | ||
| University of Puerto Rico |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29802852 | Derived | 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. |
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Subjects were screened and enrolled at the Johns Hopkins Hospital and the University of Puerto Rico Hospital.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm I (Curcumin) | Patients receive curcumin by mouth (PO) twice a day (BID) for 12 months. Curcumin: Given PO |
| FG001 | Arm II (Placebo) | Patients receive placebo PO BID for 12 months. Placebo: Given PO |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Completed 4 Months. |
|
| |||||||||||||||||||||
| Completed 8 Months. |
| ||||||||||||||||||||||
| Completed 12 Months. |
| ||||||||||||||||||||||
| Completed 16 Months. |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm I (Curcumin) | Patients receive curcumin PO BID for 12 months. Curcumin: Given PO |
| BG001 | Arm II (Placebo) | Patients receive placebo PO BID for 12 months. Placebo: Given PO |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Posted | Mean | 95% Confidence Interval | polyps | Up to 12 months |
|
|
Reported adverse events (AE) included events starting on or after day 0 and on or before month 16.
If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm I (Curcumin) | Patients receive curcumin PO BID for 12 months. Curcumin: Given PO |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | Non-systematic Assessment | Subject developed appendicitis unrelated to study drug. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Coordinator | Johns Hopkins University | 410-955-3817 | lhylind1@jhmi.edu |
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| ID | Term |
|---|---|
| D011125 | Adenomatous Polyposis Coli |
| ID | Term |
|---|---|
| D018256 | Adenomatous Polyps |
| D000236 | Adenoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D003474 | Curcumin |
| ID | Term |
|---|---|
| D036381 | Diarylheptanoids |
| D006536 | Heptanes |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
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| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Placebo | Other | Given PO |
|
|
| 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. | 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. | 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) | Baseline and 8 months |
| Change in Total Polyamines Levels | Polyamine mean level changes (expressed as pg/mg protein) at month 8-baseline | 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) | 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) | Baseline and 8 months |
| Change in Spermine Oxidase (SMOX) | Change in SMOX mean activity level at 8 months compared to baseline (time 0) | 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 | Baseline up to 8 months |
| Change in Apoptosis Index Levels | Change in apoptosis index levels at 8 months by assessing cleaved Caspase-3 measurement | 8 months |
| Baseline to up to 12 months. |
| Number of Patients Failing Study. | Patients withdrawn from study due to increasing polyp burden and/or advancing histology. | Up to 16 months. |
| Change in Vascular Density | Baseline up to 12 months |
| Activation of NFKB (Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells) Pathway | Baseline to 12 months |
| Change in Akt Phosphorylation Levels | Baseline up to 12 months |
| San Juan |
| 00936 |
| Puerto Rico |
| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Baseline number of polyps | Mean | Standard Deviation | polyps |
|
| Baseline size of polyps in mm | Mean | Standard Deviation | polyps |
|
| Participants |
|
|
|
| Secondary | Mean Polyp Size in mm | Mean size of the 5 largest polyps | Posted | Mean | 95% Confidence Interval | mm | Up to 12 months |
|
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | 12 months |
|
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | Up to 12 months |
|
|
|
|
| Secondary | 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. | Posted | Median | Full Range | percentage of total compliance | Up to 12 months |
|
|
|
|
| Secondary | 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) | Posted | Mean | Standard Deviation | nmol/mg/hr | Baseline and 8 months |
|
|
|
|
| Secondary | Change in Total Polyamines Levels | Polyamine mean level changes (expressed as pg/mg protein) at month 8-baseline | Posted | Mean | Standard Deviation | pg/mg protein | Baseline and 8 months |
|
|
|
|
| Secondary | Change in Micro RNA 124-U6 (miR124-U6) | Change in MicroRNA mean activity level at 8 months compared to baseline (time 0) | Posted | Mean | Standard Deviation | qRT-PCR relative to U6 snRNA | Baseline and 8 months |
|
|
|
|
| Secondary | Change in Spermidine/Spermine N-1 Acetyl Transferase (SSAT) | Change in SSAT mean activity level at 8 months compared to baseline (time 0) | Posted | Mean | Standard Deviation | pmol/acetylspermidine/mg protein/min | Baseline and 8 months |
|
|
|
|
| Secondary | Change in Spermine Oxidase (SMOX) | Change in SMOX mean activity level at 8 months compared to baseline (time 0) | Posted | Mean | Standard Deviation | pmol H2O2 per min per mg protein | Baseline and 8months |
|
|
|
|
| Secondary | 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 | Specimens for analysis were only available on 7 curcumin and 10 placebo participants. | Posted | Mean | Standard Deviation | labeled cells/crypt epithelial cells | Baseline up to 8 months |
|
|
|
|
| Secondary | Change in Apoptosis Index Levels | Change in apoptosis index levels at 8 months by assessing cleaved Caspase-3 measurement | Specimens for analysis were only available on 7 curcumin and 10 placebo participants. | Posted | Mean | Standard Deviation | apoptotic rate | 8 months |
|
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|
|
| Other Pre-specified | Change in Mucosal DNA Methylation Levels. | The outcome data were not collected and the outcome will never be analyzed. | Posted | Baseline to up to 12 months |
|
|
| Other Pre-specified | Change in Mucosal Leukotriene Levels. | The outcome data were not collected and the outcome will never be analyzed. | Posted | Baseline to up to 12 months. |
|
|
| Other Pre-specified | Change in Mucosal Prostaglandin Levels. | The outcome data were not collected and the outcome will never be analyzed. | Posted | Baseline to up to 12 months. |
|
|
| Other Pre-specified | Number of Patients Failing Study. | Patients withdrawn from study due to increasing polyp burden and/or advancing histology. | Posted | Count of Participants | Participants | Up to 16 months. |
|
|
|
|
| Other Pre-specified | Change in Vascular Density | Posted | Baseline up to 12 months |
|
|
| Other Pre-specified | Activation of NFKB (Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells) Pathway | Posted | Baseline to 12 months |
|
|
| Other Pre-specified | Change in Akt Phosphorylation Levels | Posted | Baseline up to 12 months |
|
|
| 0 |
| 21 |
| 3 |
| 21 |
| 8 |
| 21 |
| EG001 | Arm II (Placebo) | Patients receive placebo PO BID for 12 months. Placebo: Given PO | 0 | 23 | 1 | 23 | 13 | 23 |
|
| Facial abscess | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Iron deficiency anemia | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Cellulitis | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Herpes Zoster | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Thyroid Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
|
| Headache migraine | Vascular disorders | Non-systematic Assessment |
|
| Sinusitis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Upper respiratory infection | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Facial abscess | Infections and infestations | Non-systematic Assessment |
|
| Influenza | Infections and infestations | Non-systematic Assessment |
|
| Viral infection | Infections and infestations | Non-systematic Assessment |
|
| Urinary tract infection | Renal and urinary disorders | Non-systematic Assessment |
|
| Back strain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Plantar fascilitis | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Torn ligament | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Gout | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | Non-systematic Assessment |
|
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| D009369 | Neoplasms |
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009386 | Neoplastic Syndromes, Hereditary |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D044483 | Intestinal Polyposis |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |