Trial Outcomes & Findings for Prevention of Disease Progression in Early Stage Indolent B Cell Malignancies. (SMM) (NCT NCT00899353)

NCT ID: NCT00899353

Last Updated: 2013-12-12

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

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)

Results posted on

2013-12-12

Participant Flow

Participant milestones

Participant milestones
Measure
Omega 3 Supplementation
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.
Overall Study
STARTED
16
Overall Study
COMPLETED
11
Overall Study
NOT COMPLETED
5

Reasons for withdrawal

Reasons for withdrawal
Measure
Omega 3 Supplementation
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.
Overall Study
Adverse Event
2
Overall Study
Lost to Follow-up
1
Overall Study
Withdrawal by Subject
2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Omega 3 Supplementation
n=16 Participants
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
6 Participants
n=5 Participants
Age, Categorical
>=65 years
10 Participants
n=5 Participants
Age Continuous
68 years
STANDARD_DEVIATION 7 • n=5 Participants
Sex: Female, Male
Female
9 Participants
n=5 Participants
Sex: Female, Male
Male
7 Participants
n=5 Participants
Region of Enrollment
United States
16 participants
n=5 Participants

PRIMARY outcome

Timeframe: 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)

Population: 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

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.

Outcome measures

Outcome measures
Measure
Baseline Nuclear Factor Kappa B Activation
n=15 Participants
Baseline nuclear factor Kappa B (NFkB) activation in isolated lymphocytes from patients with early stage chronic lymphocytic leukemia.
Nuclear Factor Kappa B Activation Following 3 Capsules Per Day
n=12 Participants
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 Activation Following 6 Capsules Per Day
n=12 Participants
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 Activation Following 9 Capsules Per Day
n=10 Participants
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 Activation Post Supplement
n=8 Participants
Nuclear factor Kappa B (NFkB)activation in isolated lymphocytes from patients with early stage chronic lymphocytic leukemia following discontinued consumption of omega 3.
Fold Change in ALC-Patient 6
Fold change in ALC after omega-3 consumption as compared to baseline ALC.
Fold Change in ALC-Patient 7
Fold change in ALC after omega-3 consumption as compared to baseline ALC.
Fold Change in ALC-Patient 8
Fold change in ALC after omega-3 consumption as compared to baseline ALC.
Fold Change in ALC-Patient 9
Fold change in ALC after omega-3 consumption as compared to baseline ALC.
Fold Change in ALC-Patient 10
Fold change in ALC after omega-3 consumption as compared to baseline ALC.
Fold Change in ALC-Patient 11
Fold change in ALC after omega-3 consumption as compared to baseline ALC.
Fold Change in ALC-Patient 13
Fold change in ALC after omega-3 consumption as compared to baseline ALC.
Fold Change in ALC-Patient 14
Fold change in ALC after omega-3 consumption as compared to baseline ALC.
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.
Total Population
7.2 10^6 NFkB Luminescence units/µg protein
Standard Error 2.25 • Interval 0.945 to 231.0
4.1 10^6 NFkB Luminescence units/µg protein
Standard Error 1.53
4.2 10^6 NFkB Luminescence units/µg protein
Standard Error 1.15
0.7 10^6 NFkB Luminescence units/µg protein
Standard Error 0.94
1.5 10^6 NFkB Luminescence units/µg protein
Standard Error 0.86
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.
Higher Initial Expressers
12.8 10^6 NFkB Luminescence units/µg protein
Standard Error 2.77
7.4 10^6 NFkB Luminescence units/µg protein
Standard Error 2.41
6.4 10^6 NFkB Luminescence units/µg protein
Standard Error 1.42
0.8 10^6 NFkB Luminescence units/µg protein
Standard Error 0.20
1.6 10^6 NFkB Luminescence units/µg protein
Standard Error 1.44
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.
Lower Initial Expressers
0.8 10^6 NFkB Luminescence units/µg protein
Standard Error 0.27
0.9 10^6 NFkB Luminescence units/µg protein
Standard Error 0.37
1.5 10^6 NFkB Luminescence units/µg protein
Standard Error 0.80
0.6 10^6 NFkB Luminescence units/µg protein
Standard Error 0.11
1.3 10^6 NFkB Luminescence units/µg protein
Standard Error 1.16

PRIMARY outcome

Timeframe: Baseline, month 1, month 2, month 3, month 6, month 9, 12 months

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Baseline Nuclear Factor Kappa B Activation
n=1 Participants
Baseline nuclear factor Kappa B (NFkB) activation in isolated lymphocytes from patients with early stage chronic lymphocytic leukemia.
Nuclear Factor Kappa B Activation Following 3 Capsules Per Day
n=1 Participants
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 Activation Following 6 Capsules Per Day
n=1 Participants
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 Activation Following 9 Capsules Per Day
n=1 Participants
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 Activation Post Supplement
n=1 Participants
Nuclear factor Kappa B (NFkB)activation in isolated lymphocytes from patients with early stage chronic lymphocytic leukemia following discontinued consumption of omega 3.
Fold Change in ALC-Patient 6
n=1 Participants
Fold change in ALC after omega-3 consumption as compared to baseline ALC.
Fold Change in ALC-Patient 7
n=1 Participants
Fold change in ALC after omega-3 consumption as compared to baseline ALC.
Fold Change in ALC-Patient 8
n=1 Participants
Fold change in ALC after omega-3 consumption as compared to baseline ALC.
Fold Change in ALC-Patient 9
n=1 Participants
Fold change in ALC after omega-3 consumption as compared to baseline ALC.
Fold Change in ALC-Patient 10
n=1 Participants
Fold change in ALC after omega-3 consumption as compared to baseline ALC.
Fold Change in ALC-Patient 11
n=1 Participants
Fold change in ALC after omega-3 consumption as compared to baseline ALC.
Fold Change in ALC-Patient 13
n=1 Participants
Fold change in ALC after omega-3 consumption as compared to baseline ALC.
Fold Change in ALC-Patient 14
n=1 Participants
Fold change in ALC after omega-3 consumption as compared to baseline ALC.
The Degree of Change in Tumor Mass Measurements During and After Omega-3 Supplementation as Evaluated by Standard Clinical Tests of Disease Activity.
1.62 Fold Change
1.71 Fold Change
0.78 Fold Change
0.96 Fold Change
1.32 Fold Change
1.08 Fold Change
1.00 Fold Change
0.92 Fold Change
1.49 Fold Change
1.05 Fold Change
1.16 Fold Change
1.03 Fold Change
1.22 Fold Change

Adverse Events

Adverse Effects

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Adverse Effects
n=16 participants at risk
Serious adverse effects associated with omega 3 fatty acid consumption.
Gastrointestinal disorders
Diarrhea
25.0%
4/16 • Number of events 5
General disorders
Nausea
12.5%
2/16 • Number of events 3

Additional Information

Dr. W. Elaine Hardman

Marshall University Joan C. Edwards School of Medicine

Phone: 304-696-3721

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place