We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Treatment of Non Alcoholic Fatty Liver Disease With n-3 Fatty Acids (WELCOME)

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: NCT00760513
Recruitment Status : Completed
First Posted : September 26, 2008
Results First Posted : October 25, 2019
Last Update Posted : October 25, 2019
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
University Hospital Southampton NHS Foundation Trust

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Investigator);   Primary Purpose: Treatment
Condition Non-Alcoholic Fatty Liver Disease
Interventions Drug: OMACOR
Drug: Placebo oral capsule
Enrollment 103
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Omega 3 Fatty Acid (Fish Oil) Dummy Pill
Hide Arm/Group Description

OMACOR (alternative name: Lovaza) 4 grammes daily, oral capsule

OMACOR: 4 grammes daily, oral capsule

 4 grammes daily, oral capsule (olive oil)
Period Title: Overall Study
Started 51 52
Completed 46 45
Not Completed 5 7
Reason Not Completed
Withdrawal by Subject             5             7
Arm/Group Title Omega 3 Fatty Acid (Fish Oil) Dummy Pill Total
Hide Arm/Group Description OMACOR (alternative name: Lovaza) 4 grammes daily, oral capsule 4 grammes daily, oral capsule (olive oil) Total of all reporting groups
Overall Number of Baseline Participants 51 52 103
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 52 participants 103 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
47
  92.2%
46
  88.5%
93
  90.3%
>=65 years
4
   7.8%
6
  11.5%
10
   9.7%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 51 participants 52 participants 103 participants
48.6  (11.1) 54  (9.6) 51.3  (10.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 52 participants 103 participants
Female
26
  51.0%
17
  32.7%
43
  41.7%
Male
25
  49.0%
35
  67.3%
60
  58.3%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants
0
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United Kingdom Number Analyzed 51 participants 52 participants 103 participants
51
 100.0%
52
 100.0%
103
 100.0%
1.Primary Outcome
Title Percentage of Liver Fat
Hide Description Percentage of liver fat was measured using magnetic resonance spectroscopy at baseline and end of study. High percentage values indicate a lot of liver fat (scale from 0 to 100%). Change in liver fat percentage represented the arithmetical difference between end of study liver fat percentage minus baseline measurement of liver fat percentage change in liver fat percentage was used to test whether the intervention decreased liver fat percentage. A negative change value in liver fat percentage indicates a response to therapy. A positive change value indicates no response to therapy.
Time Frame Baseline and 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Omega 3 Fatty Acid (Fish Oil) Dummy Pill
Hide Arm/Group Description:
OMACOR (alternative name: Lovaza) 4 grammes daily, oral capsule
4 grammes daily, oral capsule (olive oil)
Overall Number of Participants Analyzed 46 45
Mean (Standard Deviation)
Unit of Measure: percentage of liver fat
-7.9  (17.4) -4.6  (9.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omega 3 Fatty Acid (Fish Oil), Dummy Pill
Comments We estimated that a 20% decrease in liver fat with Omacor treatment, assuming a sigma of 0.3, and an alpha of 0.05; with 91 participants completing our trial, we had 86% power to detect a 20% change in liver fat (two tailed test) (see HEPATOLOGY 2014;60:1211-1221).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments The a priori threshold for statistical significance = P</=0.05
Method Regression, Linear
Comments Adjusted for baseline value of liver fat percentage
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-6.3 to 3.0
Estimation Comments [Not Specified]
2.Primary Outcome
Title Liver Fibrosis Score
Hide Description The Liver Fibrosis Score is an algorithmically derived score of liver fibrosis comprising measurements of tissue matrix metalloproteinase-1 (TIMP-1), hyaluronic acid (HA) and the amino terminal end of procollagen III (PIIINP) (see Guha et al. in Reference section). The Score represents a number on a numerical scale from 0 to 20. High values of the score (measured in arbitrary units) indicate high probability of advanced liver fibrosis, low scores indicate low probability of advanced liver fibrosis. Change in Liver Fibrosis Score was used to test the intervention. Change in liver fibrosis score represented the change in measurement as calculated as the arithmetic difference between the end value minus the baseline value of the Liver Fibrosis Score. The change in Liver Fibrosis Score can therefore be negative (representing an improvement in liver fibrosis between baseline and end of study) or be positive, (representing a worsening a liver fibrosis between baseline and end of study.
Time Frame Baseline and 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with baseline and end of study data
Arm/Group Title Omega 3 Fatty Acid (Fish Oil) Dummy Pill
Hide Arm/Group Description:

OMACOR (alternative name: Lovaza) 4 grammes daily, oral capsule

OMACOR: 4 grammes daily, oral capsule

4 grammes daily, oral capsule (olive oil)

Placebo oral capsule: 4 grammes daily, oral capsule (olive oil)
Overall Number of Participants Analyzed 46 45
Mean (Standard Deviation)
Unit of Measure: score on a scale
0.3  (0.6) 0.2  (0.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omega 3 Fatty Acid (Fish Oil), Dummy Pill
Comments Based on the available evidence at the time, we assumed that a 0.6-1.0 unit change in fibrosis score might be clinically significant (Hepatology 2008 Feb;47(2):455-460). Consequently, to detect a minimum 0.6 unit change in score (e.g. 9.0 at baseline and 8.4 at the end of the study) with an SD of 1.0, 100 participants would provide >80% power at the 5% significance level, and with a 15% drop out of participants there would also be >80% power to detect this effect.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments A priori p value threshold </=0.5
Method Regression, Linear
Comments Adjusted for baseline
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.001
Confidence Interval (2-Sided) 95%
-0.3 to 0.3
Estimation Comments [Not Specified]
3.Primary Outcome
Title NAFLD Fibrosis Score
Hide Description The NAFLD fibrosis score represented a validated algorithmically-derived measure of liver fibrosis as reported in Angulo et al (see reference section). The Score is derived from anthropometric and biochemical measurements in subjects. The NAFLD fibrosis score represents an arbitrary number with no units from -5.0 to +5.0. High positive NAFLD fibrosis scores indicate a high probability of advanced liver fibrosis. Negative scores represent a low probability of advanced liver fibrosis. The change in NAFLD fibrosis score (measured in arbitrary units) was used to test the effect of the intervention and represented the arithmetic difference in the end minus baseline measurements of this score. Thus, a negative change in the Score in the Table represented an improvement in liver fibrosis score between baseline and the end of the study. A positive change in the Score in the Table represented a worsening in liver fibrosis score between baseline and end of the study.
Time Frame Baseline and 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with baseline and end of study data.
Arm/Group Title Omega 3 Fatty Acid (Fish Oil) Dummy Pill
Hide Arm/Group Description:
OMACOR (alternative name: Lovaza) 4 grammes daily, oral capsule
4 grammes daily, oral capsule (olive oil)
Overall Number of Participants Analyzed 46 45
Mean (Standard Deviation)
Unit of Measure: score on a scale
0.8  (0.9) 0.8  (0.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Omega 3 Fatty Acid (Fish Oil), Dummy Pill
Comments There was no power calculation for this end point.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9
Comments A priori threshold for statistical significance p </=0.05
Method Regression, Linear
Comments Adjusted for baseline measurement.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.4 to 0.3
Estimation Comments [Not Specified]
Time Frame 18 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Omega 3 Fatty Acid (Fish Oil) Dummy Pill
Hide Arm/Group Description

OMACOR (alternative name: Lovaza) 4 grammes daily, oral capsule

OMACOR: 4 grammes daily, oral capsule

4 grammes daily, oral capsule (olive oil)

OMACOR: 4 grammes daily, oral capsule
All-Cause Mortality
Omega 3 Fatty Acid (Fish Oil) Dummy Pill
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Omega 3 Fatty Acid (Fish Oil) Dummy Pill
Affected / at Risk (%) Affected / at Risk (%)
Total   4/51 (7.84%)   8/52 (15.38%) 
Cardiac disorders     
chest pain radiating to the neck with tingling to left arm †  0/51 (0.00%)  1/52 (1.92%) 
Endocrine disorders     
stabilisation of her diabetes †  0/51 (0.00%)  1/52 (1.92%) 
Gastrointestinal disorders     
Anaemia and disorientation †  1/51 (1.96%)  0/52 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute asthma attack †  0/51 (0.00%)  1/52 (1.92%) 
severe chest pain †  1/51 (1.96%)  0/52 (0.00%) 
Skin and subcutaneous tissue disorders     
cellulitis on right lateral malleolus †  1/51 (1.96%)  0/52 (0.00%) 
Surgical and medical procedures     
seminoma †  0/51 (0.00%)  1/52 (1.92%) 
Laparoscopy and appendectomy †  0/51 (0.00%)  1/52 (1.92%) 
laparoscopic adhesiolysis †  0/51 (0.00%)  1/52 (1.92%) 
elective hysterectomy †  0/51 (0.00%)  1/52 (1.92%) 
removal of myxoma †  0/51 (0.00%)  1/52 (1.92%) 
Tonsillectomy †  1/51 (1.96%)  0/52 (0.00%) 
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Omega 3 Fatty Acid (Fish Oil) Dummy Pill
Affected / at Risk (%) Affected / at Risk (%)
Total   49/51 (96.08%)   44/52 (84.62%) 
Blood and lymphatic system disorders     
anaemia †  2/51 (3.92%)  0/52 (0.00%) 
Cardiac disorders     
chest pain and ecg alterations †  5/51 (9.80%)  5/52 (9.62%) 
Ear and labyrinth disorders     
otolaryngological disorders †  10/51 (19.61%)  3/52 (5.77%) 
Endocrine disorders     
onset diabetes †  2/51 (3.92%)  1/52 (1.92%) 
Eye disorders     
ophtalmological disorders †  0/51 (0.00%)  6/52 (11.54%) 
Gastrointestinal disorders     
Nausea and vomitting †  3/51 (5.88%)  4/52 (7.69%) 
diarrhea †  4/51 (7.84%)  6/52 (11.54%) 
gastrointestinal disorder †  6/51 (11.76%)  5/52 (9.62%) 
proctological disorders †  3/51 (5.88%)  3/52 (5.77%) 
General disorders     
accidental fall †  0/51 (0.00%)  2/52 (3.85%) 
achile's heel and foot problems †  0/51 (0.00%)  2/52 (3.85%) 
anxiety and depression †  4/51 (7.84%)  2/52 (3.85%) 
dental disorders †  0/51 (0.00%)  2/52 (3.85%) 
fall and fracture †  1/51 (1.96%)  0/52 (0.00%) 
fluid retention and oedema †  0/51 (0.00%)  2/52 (3.85%) 
headache and dizziness †  6/51 (11.76%)  6/52 (11.54%) 
hypertension †  5/51 (9.80%)  1/52 (1.92%) 
insomnia †  1/51 (1.96%)  0/52 (0.00%) 
Hepatobiliary disorders     
hepatological disorder †  0/51 (0.00%)  1/52 (1.92%) 
liver biopsy †  1/51 (1.96%)  0/52 (0.00%) 
Infections and infestations     
chest infection †  13/51 (25.49%)  4/52 (7.69%) 
Metabolism and nutrition disorders     
dyslipidaemia †  1/51 (1.96%)  1/52 (1.92%) 
hyperglycaemia & hypoglycaemia †  1/51 (1.96%)  3/52 (5.77%) 
Musculoskeletal and connective tissue disorders     
back pain and sciatica †  3/51 (5.88%)  2/52 (3.85%) 
carpal disorders †  0/51 (0.00%)  1/52 (1.92%) 
fibromyalgia †  1/51 (1.96%)  0/52 (0.00%) 
joint pain †  13/51 (25.49%)  11/52 (21.15%) 
knee surgery †  2/51 (3.92%)  0/52 (0.00%) 
orthopedic disorder †  0/51 (0.00%)  1/52 (1.92%) 
Nervous system disorders     
neurological disorders †  1/51 (1.96%)  0/52 (0.00%) 
Product Issues     
other drug overdose †  2/51 (3.92%)  0/52 (0.00%) 
other drug reaction †  5/51 (9.80%)  0/52 (0.00%) 
Renal and urinary disorders     
urological disorders †  5/51 (9.80%)  11/52 (21.15%) 
Reproductive system and breast disorders     
fertility problems †  1/51 (1.96%)  0/52 (0.00%) 
gynecological disorders †  2/51 (3.92%)  1/52 (1.92%) 
pregnancy †  1/51 (1.96%)  0/52 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
asthma and breathing †  3/51 (5.88%)  0/52 (0.00%) 
flu, cough and sore throat †  13/51 (25.49%)  5/52 (9.62%) 
Skin and subcutaneous tissue disorders     
dermatological disorders †  8/51 (15.69%)  9/52 (17.31%) 
†
Indicates events were collected by systematic assessment
[Not Specified]
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: Professor CD Byrne
Organization: University Hospital Southampton
Phone: 02381205006
EMail: c.d.byrne@soton.ac.uk
Publications of Results:
Scorletti E, Bhatia L, McCormick KG, Clough GF, Nash K, Hodson L, Moyses HE, Calder PC, Byrne CD; WELCOME Study. Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: results from the Welcome* study. Hepatology. 2014 Oct;60(4):1211-21. doi: 10.1002/hep.27289.
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University Hospital Southampton NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT00760513    
Other Study ID Numbers: 25-12-59. (R&D: RHM MED 0836)
08/H0502/165 ( Other Identifier: Local Research Ethics Committee )
First Submitted: September 25, 2008
First Posted: September 26, 2008
Results First Submitted: January 3, 2019
Results First Posted: October 25, 2019
Last Update Posted: October 25, 2019