Trial Outcomes & Findings for Investigation of Synbiotic Treatment in NAFLD (NCT NCT01680640)

Last Updated: 2021-02-05

Results Overview

Change in liver fat percent was calculated as the percent liver fat at the end of the study, minus the percent of liver fat prior to the intervention. Change in liver fat percent ranged from -60.6% (good) to + 33.7% (bad).

Recruitment status

COMPLETED

Study phase

Target enrollment

104 participants

Primary outcome timeframe

baseline and 12 months

Results posted on

2021-02-05

Participant Flow

Participant milestones

Participant milestones
Measure	Synbiotic Fructo-oligosaccharide with a degree of polymerization \< 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day). Synbiotic: The synbiotic to be used is fructo-oligosachharide with a degree of polymerization \< 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day).	Maltodextrin 4 grams of maltodextrin daily. Maltodextrin
Overall Study STARTED	55	49
Overall Study COMPLETED	45	44
Overall Study NOT COMPLETED	10	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Investigation of Synbiotic Treatment in NAFLD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Synbiotic n=45 Participants Fructo-oligosaccharide with a degree of polymerization \< 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day). Synbiotic: The synbiotic to be used is fructo-oligosaccharide with a degree of polymerization \< 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day).	Maltodextrin n=44 Participants 4 grams of maltodextrin daily. Maltodextrin	Total n=89 Participants Total of all reporting groups
Age, Continuous	50.2 years STANDARD_DEVIATION 12.4 • n=5 Participants	51.6 years STANDARD_DEVIATION 13.1 • n=7 Participants	50.8 years STANDARD_DEVIATION 12.6 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	17 Participants n=7 Participants	31 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	27 Participants n=7 Participants	58 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	45 Participants n=5 Participants	44 Participants n=7 Participants	89 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United Kingdom	45 Participants n=5 Participants	44 Participants n=7 Participants	89 Participants n=5 Participants
percentage liver fat	26.9 percentage n=5 Participants	22.9 percentage n=7 Participants	25 percentage n=5 Participants
ELF score	6.9 units on a scale STANDARD_DEVIATION 0.4 • n=5 Participants	6.9 units on a scale STANDARD_DEVIATION 0.3 • n=7 Participants	6.9 units on a scale STANDARD_DEVIATION 0.4 • n=5 Participants
NAFLD fibrosis score	-1.3 units on a scale STANDARD_DEVIATION 1.3 • n=5 Participants	-1.2 units on a scale STANDARD_DEVIATION 1.3 • n=7 Participants	-1.2 units on a scale STANDARD_DEVIATION 1.3 • n=5 Participants
Bifidobacterium spp.	0.8 percentage n=5 Participants	0.6 percentage n=7 Participants	0.8 percentage n=5 Participants

PRIMARY outcome

Timeframe: baseline and 12 months

Population: numerical difference between baseline measurement and 12 month measurement

Outcome measures

Outcome measures
Measure	Synbiotic n=45 Participants Fructo-oligosaccharide with a degree of polymerization \< 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day). Synbiotic: The synbiotic to be used is fructo-oligosaccharide with a degree of polymerization \< 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day).	Maltodextrin n=44 Participants 4 grams of maltodextrin daily. Maltodextrin
Change in Liver Fat	-3.8 percentage of liver fat Interval -7.98 to 0.38	-6.0 percentage of liver fat Interval -10.6 to -1.45

PRIMARY outcome

Timeframe: baseline and 12 months

Population: numerical difference between baseline measurement and 12 month measurement

Change in Enhanced Liver Fibrosis score (ELF) was calculated as ELF score at the end of the study minus ELF score prior to the intervention (at baseline). A decrease in the ELF score was considered good as it reflected a decrease in liver fibrosis, and an increase in ELF score was considered bad as it reflected an increase in liver fibrosis. Change in ELF scores ranged from -0.56 (good) to + 0.68 (bad).

Outcome measures

Outcome measures
Measure	Synbiotic n=45 Participants Fructo-oligosaccharide with a degree of polymerization \< 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day). Synbiotic: The synbiotic to be used is fructo-oligosaccharide with a degree of polymerization \< 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day).	Maltodextrin n=44 Participants 4 grams of maltodextrin daily. Maltodextrin
Change in Enhanced Liver Fibrosis Score (ELF)	0.12 units on a scale Interval 0.03 to 0.19	0.13 units on a scale Interval 0.05 to 0.19

PRIMARY outcome

Timeframe: baseline and 12 months

Population: numerical difference between baseline measurement and 12 month measurement

Change in NAFLD Fibrosis Score (NFS) was calculated as the NFS score at the end of the study, minus NFS score prior to the intervention (at baseline). A decrease in the NFS score was considered good because it reflected a decrease in liver fibrosis, and an increase in NFS score was considered bad, as it reflected an increase in liver fibrosis. Change in NFS scores ranged from -2.07 (good) to + 1.75 (bad)

Outcome measures

Outcome measures
Measure	Synbiotic n=45 Participants Fructo-oligosaccharide with a degree of polymerization \< 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day). Synbiotic: The synbiotic to be used is fructo-oligosaccharide with a degree of polymerization \< 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day).	Maltodextrin n=44 Participants 4 grams of maltodextrin daily. Maltodextrin
Change in NAFLD Fibrosis Score	-1.3 units on a scale Interval -1.68 to -0.92	-1.2 units on a scale Interval -1.58 to -0.82

PRIMARY outcome

Timeframe: baseline and 12 months

Population: numerical difference between baseline measurement and 12 month measurement

The change in percent of Bifidobacteria spp was computed as the percent of Bifidobactera spp at the end of the study minus the percent of Bifidobacteria prior to the intervention (at baseline). A positive change in percent (e.g +0.1 to 7.0%) in Bifidobacteria spp. was considered good and a negative change in percent (e.g. -0.1 to -0.5%) in Bifidobacteria spp. considered bad. (Minimum = -0.5% (bad) and Maximum = +7.0% (good)).

Outcome measures

Outcome measures
Measure	Synbiotic n=45 Participants Fructo-oligosaccharide with a degree of polymerization \< 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day). Synbiotic: The synbiotic to be used is fructo-oligosaccharide with a degree of polymerization \< 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day).	Maltodextrin n=44 Participants 4 grams of maltodextrin daily. Maltodextrin
Change in Bifidobacterium Spp.	1.72 percentage of fecal Bifidobacterium spp Interval 0.89 to 2.55	-0.02 percentage of fecal Bifidobacterium spp Interval -0.46 to 0.42

Adverse Events

Synbiotic

Serious events: 6 serious events

Other events: 35 other events

Deaths: 0 deaths

Maltodextrin

Serious events: 6 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Synbiotic n=55 participants at risk Fructo-oligosaccharide with a degree of polymerization \< 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day). Synbiotic: The synbiotic to be used is fructo-oligosaccharide with a degree of polymerization \< 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day).	Maltodextrin n=49 participants at risk 4 grams of maltodextrin daily. Maltodextrin
Investigations Back pain after Liver biopsy	0.00% 0/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	2.0% 1/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Cardiac disorders myocardial infarction	0.00% 0/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	2.0% 1/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
General disorders abdominal pain, surgery	3.6% 2/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	4.1% 2/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Reproductive system and breast disorders breast cancer	1.8% 1/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	0.00% 0/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Musculoskeletal and connective tissue disorders orthopedic	5.5% 3/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	4.1% 2/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Renal and urinary disorders urinary tract cancer	1.8% 1/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	0.00% 0/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
General disorders Hypertension	0.00% 0/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	2.0% 1/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Respiratory, thoracic and mediastinal disorders chest infection	3.6% 2/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	0.00% 0/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.

Other adverse events

Additional Information

Christopher D Byrne

University of Southampton

Phone: 44 (0)23 8120 8818

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Synbiotic n=55 participants at risk Fructo-oligosaccharide with a degree of polymerization \< 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day). Synbiotic: The synbiotic to be used is fructo-oligosaccharide with a degree of polymerization \< 10 at 4 g/twice a day (two sticks a day) plus Bifidobacterium animalis subsp. lactis BB-12 as minimum of 10 billion CFU/day (1 capsule a day).	Maltodextrin n=49 participants at risk 4 grams of maltodextrin daily. Maltodextrin
Surgical and medical procedures Post adipose tissue biopsy pain	3.6% 2/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	4.1% 2/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Gastrointestinal disorders diverticulosis, intestinal disorders	5.5% 3/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	6.1% 3/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Gastrointestinal disorders Nausea, vomitting and diarrhea	21.8% 12/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	20.4% 10/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
General disorders Headache, collapse, dizziness	9.1% 5/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	12.2% 6/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Respiratory, thoracic and mediastinal disorders Flu, chest infection	25.5% 14/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	26.5% 13/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Skin and subcutaneous tissue disorders dermatological problems	3.6% 2/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	2.0% 1/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
General disorders dental problems	7.3% 4/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	2.0% 1/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
General disorders anxiety and depression	1.8% 1/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	8.2% 4/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Hepatobiliary disorders Liver alteration other than NAFLD	3.6% 2/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	2.0% 1/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Musculoskeletal and connective tissue disorders Joint pain, back pain	34.5% 19/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	32.7% 16/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Skin and subcutaneous tissue disorders Skin infection, abrasion, rash	14.5% 8/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	14.3% 7/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Renal and urinary disorders urinary tract disorders	12.7% 7/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	2.0% 1/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Cardiac disorders chest pain, alterations on ecg	5.5% 3/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	2.0% 1/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Metabolism and nutrition disorders Hyperglycaemia	1.8% 1/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	0.00% 0/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Vascular disorders vascular disorders	1.8% 1/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	2.0% 1/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Ear and labyrinth disorders otorhinolaryngological disorders	3.6% 2/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	2.0% 1/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
General disorders hypertension	0.00% 0/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	2.0% 1/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Reproductive system and breast disorders breast disorders	1.8% 1/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	0.00% 0/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Metabolism and nutrition disorders nutrient deficiency	1.8% 1/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	0.00% 0/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.
Eye disorders ophtalmology disorders	1.8% 1/55 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.	0.00% 0/49 • The adverse event data were collected over the period of the study between baseline and end of study (total period 12 months). We used the clinicaltrials.gov definition for adverse event and/or serious adverse event.