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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00899353
Recruitment Status : Terminated (Original Principal Investigator left the institution.)
First Posted : May 12, 2009
Results First Posted : November 18, 2013
Last Update Posted : December 12, 2013
Sponsor:
Collaborator:
Edwards Foundation, Inc.
Information provided by (Responsible Party):
W. Elaine Hardman, Ph.D., Marshall University

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Monoclonal Gammopathy of Undetermined Significance
Smoldering Multiple Myeloma
Chronic Lymphocytic Leukemia
Intervention Dietary Supplement: Omega 3 Fatty Acid
Enrollment 16
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Omega 3 Supplementation
Hide 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
Reason Not Completed
Adverse Event             2
Lost to Follow-up             1
Withdrawal by Subject             2
Arm/Group Title Omega 3 Supplementation
Hide Arm/Group Description [Not Specified]
Overall Number of Baseline Participants 16
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
<=18 years
0
   0.0%
Between 18 and 65 years
6
  37.5%
>=65 years
10
  62.5%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants
68  (7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
Female
9
  56.3%
Male
7
  43.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 16 participants
16
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.
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 15 12 12 10 8
Mean (Standard Error)
Unit of Measure: 10^6 NFkB Luminescence units/µg protein
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)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.78
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.75
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.08
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.17
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.61
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.32
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.88
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.98
Comments [Not Specified]
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 [Not Specified]
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.98
Comments [Not Specified]
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 [Not Specified]
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.
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 1 1 1 1 1 1 1 1 1 1 1 1 1
Measure Type: Number
Unit of Measure: 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
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Adverse Effects
Hide Arm/Group Description Serious adverse effects associated with omega 3 fatty acid consumption.
All-Cause Mortality
Adverse Effects
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Adverse Effects
Affected / at Risk (%) # Events
Total   0/16 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Adverse Effects
Affected / at Risk (%) # Events
Total   5/16 (31.25%)    
Gastrointestinal disorders   
Diarrhea * [1]  4/16 (25.00%)  5
General disorders   
Nausea * [2]  2/16 (12.50%)  3
*
Indicates events were collected by non-systematic assessment
[1]
Grade 1 and 2 Diarrhea in participants consuming 6 or 9 capsules per day (4.8 or 7.2g per day)
[2]
Participants were consuming 6 or 9 capsules per day (4.8 or 7.2g per day)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. W. Elaine Hardman
Organization: Marshall University Joan C. Edwards School of Medicine
Phone: 304-696-3721
EMail: hardmanw@marshall.edu
Layout table for additonal information
Responsible Party: W. Elaine Hardman, Ph.D., Marshall University
ClinicalTrials.gov Identifier: NCT00899353    
Other Study ID Numbers: MU9230
First Submitted: May 8, 2009
First Posted: May 12, 2009
Results First Submitted: April 29, 2013
Results First Posted: November 18, 2013
Last Update Posted: December 12, 2013