Prevention of Disease Progression in Early Stage Indolent B Cell Malignancies. (SMM)

• Sponsor: Marshall University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00899353
• Collaborator: Edwards Foundation, Inc. (Other)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 50
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Escalating doses of Omega 3 Fatty Acids are being used in patients who have early stage Chronic Lymphocytic Leukemia (ES-CLL), Monoclonal Gammopathy of Undetermined Significance (MGUS), or Smoldering Multiple Myeloma (SMM), whose disease does not currently require treatment. The primary aim of the study is to determine if the Omega 3 supplementation will help prevent or delay progression of the disease to a stage that requires treatment.

Condition or Disease	Intervention/Treatment	Phase
Monoclonal Gammopathy of Undetermined Significance; Smoldering Multiple Myeloma; Chronic Lymphocytic Leukemia	Dietary Supplement: Omega 3 Fatty Acid	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Inhibition of Nuclear Factor Kappa B for Prevention of Disease Progression in Indolent B Cell Malignancies
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Omega 3 supplement Omega 3 supplement will be added to diet, 3 capsules per day for one month then 6 capsules per day for one month then 9 capsules per day as tolerated	Dietary Supplement: Omega 3 Fatty Acid; Omega 3 supplementation will be initiated at three 1250 mg capsules daily for the first month. If dose is well tolerated, it will be increased to six 1250 mg capsules daily for 30 days, and finally to nine 1250 mg capsules daily. Treatment period is 12 months.; Other Names: Res-Q® 1250

Outcome Measures

Primary Outcome Measures

1. Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement. [baseline, and post supplement month 1(3 capsules/day), month 2 (6capsules/day), month 3 (9 capusules/day), month 6 (9 capusules/day), month 9 (9 capusules/day), month 12 (post supplement)]

   Peripheral lymphocytes were isolated from the blood using Ficoll-Paque gradient. Nuclear Factor Kappa B activation was analyzed using Thermo Scientific Transcription Factor kit for NFkB p50, according to manufacturer's protocol. Protein extracts containing 1-15µg of protein/well were added in triplicates. Luminescence resulting from a reaction with bound NFkB was detected using a Berthold Centro LB960 Luminometer and analyzed with MikroWin 2000 ver. 1.08. NFkB activity was normalized by luminescence units/µg of protein per well.

2. The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity. [Baseline, month 1, month 2, month 3, month 6, month 9, 12 months]

   Patients diagnosed with early stage (asymptomatic) CLL were supplemented with escalating doses of omega-3 (n-3) fatty acids (2.4 g of n-3/day up to 7.2 g of n-3/day). Given that these patients are asymptomatic and did not require treatment, measures of tumor mass during and after omega-3 supplementation, as evaluated by standard clinical tests of disease activity, were not performed. Instead, absolute lymphocyte counts (ALC), as a measure of tumor burden, was evaluated before and after omega-3 supplementation. Data represents the fold change in ALC post omega-3 consumption as compared to baseline ALC. Patients with MGUS or SMM were not enrolled into this study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must be over 18 years of age.

• Must be free of other medical conditions that would decrease life expectancy to less that 12 months.

• Must be free of Omega 3 supplements or other fish oil containing nutritional supplements for a minimum of two months prior to enrollment.

• Must have a ECOG performance status of 0,1 or 2.

Exclusion Criteria:

• Any life-threatening condition such as (but not limited to) advanced heart disease, kidney or liver failure with an expected survival of less than 12 months.

• Any other active malignancy.

• Women who are pregnant or lactating.

• Individuals unable to give informed consent.

• Individuals with known allergy or intolerance to fish oil supplements.

• Any patient with an active bleeding diatheses or disorder.

• ECOG performance status of 3 or 4.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Edwards Comprehensive Cancer Center	Huntington	West Virginia	United States	25701

Sponsors and Collaborators

• Marshall University
• Edwards Foundation, Inc.

Investigators

• Principal Investigator: Wanda E Hardman, Ph.D., Professor Marshall University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: W. Elaine Hardman, Ph.D., W. Elaine Hardman, Ph.D., Marshall University School of Medicine, Professor of Biochemistry and Microbiology, Marshall University
• ClinicalTrials.gov Identifier: NCT00899353
• Other Study ID Numbers: MU9230
• First Posted: May 12, 2009
• Last Update Posted: Dec 12, 2013
• Last Verified: Nov 1, 2013

• Keywords provided by W. Elaine Hardman, Ph.D., W. Elaine Hardman, Ph.D., Marshall University School of Medicine, Professor of Biochemistry and Microbiology, Marshall University: ES-CLL; MGUS; SMM; Early Stage - Chronic Lymphocytic Leukemia
• Additional relevant MeSH terms: Multiple Myeloma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Smoldering Multiple Myeloma; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance; Disease Progression

Study Results

Participant Flow

Arm/Group Title	Omega 3 Supplementation
Arm/Group Description	Baseline blood specimens were obtained. All participants were then assigned to consume three, 1250mg omega 3 supplement capsules per day (providing 2.4g of omega 3 total) for one month, the first period. Blood was obtained and participants were assigned to consume six, 1250mg capsules of omega 3 per day (providing 4.8g of omega 3)for one month, the second period. Blood was again obtained and participants were assigned to consume 9 capsules of omega 3 per day, providing 7.2g of omega 3,the third period.
Period Title: Overall Study
STARTED	16
COMPLETED	11
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Omega 3 Supplementation
Arm/Group Description
Overall Participants	16
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 37.5%
>=65 years	10 62.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68 (7)
Sex: Female, Male (Count of Participants)
Female	9 56.3%
Male	7 43.8%
Region of Enrollment (participants) [Number]
United States	16 100%

Outcome Measures

1. Primary Outcome

Title	Activated Nuclear Factor Kappa B (NFkB) in Peripheral Blood Lymphocytes From Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) Before, During and After Consumption of an Omega 3 Supplement.
Description	Peripheral lymphocytes were isolated from the blood using Ficoll-Paque gradient. Nuclear Factor Kappa B activation was analyzed using Thermo Scientific Transcription Factor kit for NFkB p50, according to manufacturer's protocol. Protein extracts containing 1-15µg of protein/well were added in triplicates. Luminescence resulting from a reaction with bound NFkB was detected using a Berthold Centro LB960 Luminometer and analyzed with MikroWin 2000 ver. 1.08. NFkB activity was normalized by luminescence units/µg of protein per well.
Time Frame	baseline, and post supplement month 1(3 capsules/day), month 2 (6capsules/day), month 3 (9 capusules/day), month 6 (9 capusules/day), month 9 (9 capusules/day), month 12 (post supplement)

Outcome Measure Data

Analysis Population Description

NFkB activation of all patients diagnosed with early stage CLL at baseline and following omega 3 consumption. Patients are further separated into high (> median, n=7) and low initial baseline (< median, n=6) NFkB. Patients included must have had one baseline and at least one period of omega 3 consumption. Not all patients completed all periods

Arm/Group Title	Baseline Nuclear Factor Kappa B Activation	Nuclear Factor Kappa B Activation Following 3 Capsules Per Day	Nuclear Factor Kappa B Activation Following 6 Capsules Per Day	Nuclear Factor Kappa B Activation Following 9 Capsules Per Day	Nuclear Factor Kappa B Activation Post Supplement
Arm/Group Description	Baseline nuclear factor Kappa B (NFkB) activation in isolated lymphocytes from patients with early stage chronic lymphocytic leukemia.	Nuclear factor Kappa B (NFkB)activation in isolated lymphocytes from patients with early stage chronic lymphocytic leukemia following consumption of 3 capsules per day (2.4 g of omega 3 per day). Each 1250mg capsule provided 800mg of omega 3.	Nuclear factor Kappa B (NFkB)activation in isolated lymphocytes from patients with early stage chronic lymphocytic leukemia following consumption of 6 capsules per day (4.8 g of omega 3 per day).Each 1250mg capsule provided 800mg of omega 3.	Nuclear factor Kappa B (NFkB)activation in isolated lymphocytes from patients with early stage chronic lymphocytic leukemia following consumption of 9 capsules per day (7.2 g of omega 3 per day). Each 1250mg capsule provided 800mg of omega 3.	Nuclear factor Kappa B (NFkB)activation in isolated lymphocytes from patients with early stage chronic lymphocytic leukemia following discontinued consumption of omega 3.
Measure Participants	15	12	12	10	8
Total Population	7.2 (2.25)	4.1 (1.53)	4.2 (1.15)	0.7 (0.94)	1.5 (0.86)
Higher Initial Expressers	12.8 (2.77)	7.4 (2.41)	6.4 (1.42)	0.8 (0.20)	1.6 (1.44)
Lower Initial Expressers	0.8 (0.27)	0.9 (0.37)	1.5 (0.80)	0.6 (0.11)	1.3 (1.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baseline Nuclear Factor Kappa B Activation, Nuclear Factor Kappa B Activation Following 3 Capsules Per Day
	Comments	Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α< 0.05. Analysis based on global response.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments
	Method	ANOVA
	Comments	Games-Howell Correction was applied to adjust for unequal variances, unequal sample size and for non-parametric distribution.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.1
	Confidence Interval	(2-Sided) 95%; -5.0 to 11.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.7
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Baseline Nuclear Factor Kappa B Activation, Nuclear Factor Kappa B Activation Following 6 Capsules Per Day
	Comments	Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α< 0.05. Analysis based on global response.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.75
	Comments
	Method	ANOVA
	Comments	Games-Howell Correction was applied to adjust for unequal variances, unequal sample size and for non-parametric distribution.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.0
	Confidence Interval	(2-Sided) 95%; -4.6 to 10.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.5
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Baseline Nuclear Factor Kappa B Activation, Nuclear Factor Kappa B Activation Following 9 Capsules Per Day
	Comments	Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α< 0.05. Analysis based on global response.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments
	Method	ANOVA
	Comments	Games-Howell Correction was applied to adjust for unequal variances, unequal sample size and for non-parametric distribution.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.6
	Confidence Interval	(2-Sided) 95%; -0.6 to 13.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.3
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Baseline Nuclear Factor Kappa B Activation, Nuclear Factor Kappa B Activation Post Supplement
	Comments	Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α< 0.05. Analysis based on global response.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	ANOVA
	Comments	Games-Howell Correction was applied to adjust for unequal variances, unequal sample size and for non-parametric distribution.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.8
	Confidence Interval	(2-Sided) 95%; -1.6 to 13.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.4
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Baseline Nuclear Factor Kappa B Activation, Nuclear Factor Kappa B Activation Following 3 Capsules Per Day
	Comments	Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α< 0.05. Analysis based on High Initial NFkB Activation Expressers.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.61
	Comments
	Method	ANOVA
	Comments	Games-Howell Correction was applied to adjust for unequal variances, unequal sample size and for non-parametric distribution.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.3
	Confidence Interval	(2-Sided) 95%; -6.5 to 17.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.7
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Baseline Nuclear Factor Kappa B Activation, Nuclear Factor Kappa B Activation Following 6 Capsules Per Day
	Comments	Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α< 0.05. Analysis based on High Initial NFkB Activation Expressers.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments
	Method	ANOVA
	Comments	Games-Howell Correction was applied to adjust for unequal variances, unequal sample size and for non-parametric distribution.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.3
	Confidence Interval	(2-Sided) 95%; -4.1 to 16.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.1
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Baseline Nuclear Factor Kappa B Activation, Nuclear Factor Kappa B Activation Following 9 Capsules Per Day
	Comments	Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α< 0.05. Analysis based on High Initial NFkB Activation Expressers.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	ANOVA
	Comments	Games-Howell Correction was applied to adjust for unequal variances, unequal sample size and for non-parametric distribution.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	12.0
	Confidence Interval	(2-Sided) 95%; 1.6 to 22.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.8
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Baseline Nuclear Factor Kappa B Activation, Nuclear Factor Kappa B Activation Post Supplement
	Comments	Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α< 0.05. Analysis based on High Initial NFkB Activation Expressers.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	ANOVA
	Comments	Games-Howell Correction was applied to adjust for unequal variances, unequal sample size and for non-parametric distribution.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	11.1
	Confidence Interval	(2-Sided) 95%; 0.5 to 21.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.1
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Baseline Nuclear Factor Kappa B Activation, Nuclear Factor Kappa B Activation Following 3 Capsules Per Day
	Comments	Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α< 0.05. Analysis based on Low Initial NFkB Activation Expressers.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	ANOVA
	Comments	Games-Howell Correction was applied to adjust for unequal variances, unequal sample size and for non-parametric distribution.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -1.5 to 1.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Baseline Nuclear Factor Kappa B Activation, Nuclear Factor Kappa B Activation Following 6 Capsules Per Day
	Comments	Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α< 0.05. Analysis based on Low Initial NFkB Activation Expressers.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.88
	Comments
	Method	ANOVA
	Comments	Games-Howell Correction was applied to adjust for unequal variances, unequal sample size and for non-parametric distribution.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -3.5 to 2.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Baseline Nuclear Factor Kappa B Activation, Nuclear Factor Kappa B Activation Following 9 Capsules Per Day
	Comments	Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α< 0.05. Analysis based on Low Initial NFkB Activation Expressers.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.98
	Comments
	Method	ANOVA
	Comments	Games-Howell Correction was applied to adjust for unequal variances, unequal sample size and for non-parametric distribution.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -0.8 to 1.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Baseline Nuclear Factor Kappa B Activation, Nuclear Factor Kappa B Activation Post Supplement
	Comments	Omnibus analysis. Statistical significance was determined by Games Howell Multiple Comparison test. Significance was determined as α< 0.05. Analysis based on Low Initial NFkB Activation Expressers.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.98
	Comments
	Method	ANOVA
	Comments	Games-Howell Correction was applied to adjust for unequal variances, unequal sample size and for non-parametric distribution.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -6.6 to 5.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.2
	Estimation Comments

2. Primary Outcome

Title	The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity.
Description	Patients diagnosed with early stage (asymptomatic) CLL were supplemented with escalating doses of omega-3 (n-3) fatty acids (2.4 g of n-3/day up to 7.2 g of n-3/day). Given that these patients are asymptomatic and did not require treatment, measures of tumor mass during and after omega-3 supplementation, as evaluated by standard clinical tests of disease activity, were not performed. Instead, absolute lymphocyte counts (ALC), as a measure of tumor burden, was evaluated before and after omega-3 supplementation. Data represents the fold change in ALC post omega-3 consumption as compared to baseline ALC. Patients with MGUS or SMM were not enrolled into this study.
Time Frame	Baseline, month 1, month 2, month 3, month 6, month 9, 12 months

Outcome Measure Data

Analysis Population Description

Patients who's absolute lymphocyte counts were known prior to omega-3 initiation (baseline) and after omega-3 consumption were included in this analysis. Patients who's ALC was unknown prior to omega-3 initiation or after omega-3 consumption were excluded.

Arm/Group Title	Fold Change in ALC-Patient 1	Fold Change in ALC-Patient 2	Fold Change in ALC-Patient 3	Fold Change in ALC-Patient 4	Fold Change in ALC-Patient 5	Fold Change in ALC-Patient 6	Fold Change in ALC-Patient 7	Fold Change in ALC-Patient 8	Fold Change in ALC-Patient 9	Fold Change in ALC-Patient 10	Fold Change in ALC-Patient 11	Fold Change in ALC-Patient 13	Fold Change in ALC-Patient 14
Arm/Group Description	Fold change in ALC after omega-3 consumption as compared to baseline ALC.	Fold change in ALC after omega-3 consumption as compared to baseline ALC.	Fold change in ALC after omega-3 consumption as compared to baseline ALC.	Fold change in ALC after omega-3 consumption as compared to baseline ALC.	Fold change in ALC after omega-3 consumption as compared to baseline ALC.	Fold change in ALC after omega-3 consumption as compared to baseline ALC.	Fold change in ALC after omega-3 consumption as compared to baseline ALC.	Fold change in ALC after omega-3 consumption as compared to baseline ALC.	Fold change in ALC after omega-3 consumption as compared to baseline ALC.	Fold change in ALC after omega-3 consumption as compared to baseline ALC.	Fold change in ALC after omega-3 consumption as compared to baseline ALC.	Fold change in ALC after omega-3 consumption as compared to baseline ALC.	Fold change in ALC after omega-3 consumption as compared to baseline ALC.
Measure Participants	1	1	1	1	1	1	1	1	1	1	1	1	1
Number [Fold Change]	1.62	1.71	0.78	0.96	1.32	1.08	1.00	0.92	1.49	1.05	1.16	1.03	1.22

Adverse Events

Arm/Group Title	Adverse Effects
Arm/Group Description	Serious adverse effects associated with omega 3 fatty acid consumption.
All Cause Mortality
	Adverse Effects
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Adverse Effects
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Other (Not Including Serious) Adverse Events
	Adverse Effects
	Affected / at Risk (%)	# Events
Total	5/16 (31.3%)
Gastrointestinal disorders
Diarrhea	4/16 (25%)	5
General disorders
Nausea	2/16 (12.5%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.