Familial Adenomatous Polyposis
Conditions
Keywords
Polyp, Familial Adenomatous Polyposis, Prevention
Brief summary
This is a 36 week dietary intervention pilot study to evaluate the effects of lyophilized black raspberries on rectal polyp burden and biomarkers in subjects with FAP. Subjects will undergo a colonoscopy or sigmoidoscopy before study treatment to determine eligibility for the study. Eligible participants will undergo a sigmoidoscopy at 36 weeks after the initiation of study treatment. The size and number of rectal polyps will be documented on a code sheet and by photograph. The efficacy outcome will include the percentage reduction in the number of rectal polyps between baseline and 36 weeks.
Interventions
DRUGBlack raspberry (BRB) Slurry
20 grams BRB Slurry
DRUGBlack Raspberry (BRB) Suppositories
Two, 730 mg BRB suppositories QHS
DRUGBlack Raspberry (BRB) Placebo Slurry
20 grams BRB placebo slurry
Sponsors
Ohio State University Comprehensive Cancer Center
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of familial adenomatous polyposis with at least 5 rectal polyps which are greater than or equal to 2 mm on baseline colonoscopy * Have an endoscopically assessable rectal segment * Have not taken NSAIDs or selective COX-2 inhibitors for two months prior to the study and willing to remain off NSAIDs for the study duration.
Exclusion criteria
* Known allergies or hypersensitivity to berries * Diabetes mellitus * Subjects taking NSAIDs or COX-2 inhibitors who cannot be taken off the medication due to their clinical condition.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End of Study in Number of Rectal Polyps | Baseline and 36 weeks | — |
| Change in Burden of Rectal Polyps | Baseline and 36 weeks | The burden was measured as the sum of the number of polyps x size of polyps in mm. The change in burden was determined between baseline and 36 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apoptosis and Cell Proliferation Measured by Percent Difference in Staining. | baseline and 36 weeks | A pooled analysis of all participants was used for biomarker results. Tissue from normal mucosa and rectal polyps were obtained to assay KI 67 (proliferation) and TUNEL at baseline and end of treatment. A decrease in the value of KI 67 implies lower proliferation while an increase in TUNEL is suggestive of an increase in apoptosis. |
Countries
United States
Participant flow
Recruitment details
Study was open for enrollment at Cleveland Clinic from December 9, 2005 to March 26, 2008. Subjects with FAP who had an assessable rectal segment were screened for potential eligibility. Once it was determined the subjects were potentially eligible they were contacted by phone or letter.
Pre-assignment details
After potentially eligible subjects signed the informed consent, a physical examination with medical history and colonoscopy or sigmoidoscopy was performed as indicated. Blood and urine samples were collected. Subjects with adequate rectal polyp burden and laboratory results within study guidelines were eligible to be randomized.
Participants by arm
| Arm | Count |
|---|---|
| Two Berry Suppositories Bedtime Plus Oral Berry Powder 20 g of lyophilized berry powder administered orally 3 times per day, plus 2 berry suppositories administered at bedtime. Each suppository contains 730 mg Black Raspberries | 12 |
| Two Berry Suppositories Bedtime Plus Placebo Powder 20 g of placebo powder administered as an oral slurry 3 times per day, plus 2 berry suppositories administered at bedtime. Each suppository contains 730 mg Black Raspberries | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 5 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Two Berry Suppositories Bedtime Plus Placebo Powder | Total | Two Berry Suppositories Bedtime Plus Oral Berry Powder |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 23 Participants | 11 Participants |
| Region of Enrollment United States | 12 participants | 24 participants | 12 participants |
| Sex: Female, Male Female | 7 Participants | 14 Participants | 7 Participants |
| Sex: Female, Male Male | 5 Participants | 10 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 12 | 10 / 12 |
| serious Total, serious adverse events | 0 / 12 | 1 / 12 |
Outcome results
Primary
Change From Baseline to End of Study in Number of Rectal Polyps
Time frame: Baseline and 36 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lyophilized Black Raspberry (BRB) Suppositories Plus Placebo | Change From Baseline to End of Study in Number of Rectal Polyps | -5.4 polyps | Standard Deviation 5.3 |
| Lypholized BRB Suppositiry Plus BRB Slurry | Change From Baseline to End of Study in Number of Rectal Polyps | -1.6 polyps | Standard Deviation 9.2 |
| All Participants | Change From Baseline to End of Study in Number of Rectal Polyps | -3.5 polyps | Standard Deviation 7.5 |
Comparison: All patients received BRB suppositories and were pooled for the analysis comparing baseline and end of study polyp counts.p-value: 0.065Wilcoxon (Mann-Whitney)
Primary
Change in Burden of Rectal Polyps
The burden was measured as the sum of the number of polyps x size of polyps in mm. The change in burden was determined between baseline and 36 weeks.
Time frame: Baseline and 36 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lyophilized Black Raspberry (BRB) Suppositories Plus Placebo | Change in Burden of Rectal Polyps | -13 polyp number x mm | Standard Deviation 11.7 |
| Lypholized BRB Suppositiry Plus BRB Slurry | Change in Burden of Rectal Polyps | -5.7 polyp number x mm | Standard Deviation 26.6 |
| All Participants | Change in Burden of Rectal Polyps | -9.4 polyp number x mm | Standard Deviation 20.1 |
p-value: 0.043Wilcoxon (Mann-Whitney)
Secondary
Apoptosis and Cell Proliferation Measured by Percent Difference in Staining.
A pooled analysis of all participants was used for biomarker results. Tissue from normal mucosa and rectal polyps were obtained to assay KI 67 (proliferation) and TUNEL at baseline and end of treatment. A decrease in the value of KI 67 implies lower proliferation while an increase in TUNEL is suggestive of an increase in apoptosis.
Time frame: baseline and 36 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lyophilized Black Raspberry (BRB) Suppositories Plus Placebo | Apoptosis and Cell Proliferation Measured by Percent Difference in Staining. | KI 67 assay at baseline | 11.3 percentage of brown staining of cells | Standard Deviation 1.14 |
| Lyophilized Black Raspberry (BRB) Suppositories Plus Placebo | Apoptosis and Cell Proliferation Measured by Percent Difference in Staining. | KI 67 at 36 weeks | 8.00 percentage of brown staining of cells | Standard Deviation 1.07 |
| Lyophilized Black Raspberry (BRB) Suppositories Plus Placebo | Apoptosis and Cell Proliferation Measured by Percent Difference in Staining. | Difference in means of KI 67 | -3.30 percentage of brown staining of cells | Standard Deviation 1.23 |
| Lyophilized Black Raspberry (BRB) Suppositories Plus Placebo | Apoptosis and Cell Proliferation Measured by Percent Difference in Staining. | Tunel assay at baseline | 0.58 percentage of brown staining of cells | Standard Deviation 0.1 |
| Lyophilized Black Raspberry (BRB) Suppositories Plus Placebo | Apoptosis and Cell Proliferation Measured by Percent Difference in Staining. | Tunel assay at 36 weeks | 1.08 percentage of brown staining of cells | Standard Deviation 0.33 |
| Lyophilized Black Raspberry (BRB) Suppositories Plus Placebo | Apoptosis and Cell Proliferation Measured by Percent Difference in Staining. | Difference in mean of Tunel | 0.50 percentage of brown staining of cells | Standard Deviation 0.33 |
| Lypholized BRB Suppositiry Plus BRB Slurry | Apoptosis and Cell Proliferation Measured by Percent Difference in Staining. | Tunel assay at 36 weeks | 7.64 percentage of brown staining of cells | Standard Deviation 1.17 |
| Lypholized BRB Suppositiry Plus BRB Slurry | Apoptosis and Cell Proliferation Measured by Percent Difference in Staining. | KI 67 assay at baseline | 55.2 percentage of brown staining of cells | Standard Deviation 2.81 |
| Lypholized BRB Suppositiry Plus BRB Slurry | Apoptosis and Cell Proliferation Measured by Percent Difference in Staining. | Tunel assay at baseline | 4.49 percentage of brown staining of cells | Standard Deviation 0.95 |
| Lypholized BRB Suppositiry Plus BRB Slurry | Apoptosis and Cell Proliferation Measured by Percent Difference in Staining. | KI 67 at 36 weeks | 49.12 percentage of brown staining of cells | Standard Deviation 2.28 |
| Lypholized BRB Suppositiry Plus BRB Slurry | Apoptosis and Cell Proliferation Measured by Percent Difference in Staining. | Difference in mean of Tunel | 3.15 percentage of brown staining of cells | Standard Deviation 1.2 |
| Lypholized BRB Suppositiry Plus BRB Slurry | Apoptosis and Cell Proliferation Measured by Percent Difference in Staining. | Difference in means of KI 67 | -6.08 percentage of brown staining of cells | Standard Deviation 1.83 |
p-value: 0.016Chi-squared