Trial Outcomes & Findings for Impact of Fructose on Metabolism, Energy Homeostasis and Magnetic Resonance Biomarkers in Nonalcoholic Fatty Liver Disease (NCT NCT01930123)
NCT ID: NCT01930123
Last Updated: 2022-08-31
Results Overview
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
118 participants
Primary outcome timeframe
Baseline to approximately one hour post-fructose administration
Results posted on
2022-08-31
Participant Flow
Subjects recruited prior to liver biopsy between November 2014 and January 2020.
Participant milestones
| Measure |
Patients With NAFLD
Subjects with biopsy-proven NAFLD; subjects will be challenged with a fructose infusion after a period for 12 hours fasting.
intravenous fructose challenge: Patients will be admitted to our Duke Clinical Research Unit (DCRU) at least 12 hours prior to morning intravenous fructose challenge. All patients will have a "standard" meal in order to control for dietary composition and calorie intake prior to intravenous fructose challenge. Patients will be NPO (nothing by mouth) after midnight for morning IV fructose MR biomarker measures. Patients with suspected NAFLD will have had an historical standard of care liver biopsy in the past and will have IV fructose Magnetic Resonance biomarker measures in the morning.
Blood Draw: Fasting bloodwork will be obtained before and after the IV fructose challenge.
|
Healthy Controls
Healthy controls for comparison with NAFLD patients.The 15 subjects will be challenged with a fructose infusion after a period for 12 hours fasting.
Intravenous fructose challenge: Patients will be admitted to our Duke Clinical Research Unit (DCRU) at least 12 hours prior to morning intravenous fructose challenge. All patients will have a "standard" meal in order to control for dietary composition and calorie intake prior to intravenous fructose challenge. Patients will be NPO (nothing by mouth) after midnight for morning IV fructose MR biomarker measures. Patients with suspected NAFLD will have had an historical standard of care liver biopsy in the past and will have IV fructose Magnetic Resonance biomarker measures in the morning.
Blood Draw: Fasting bloodwork will be obtained before and after the IV fructose challenge.
|
|---|---|---|
|
Overall Study
STARTED
|
81
|
37
|
|
Overall Study
COMPLETED
|
58
|
29
|
|
Overall Study
NOT COMPLETED
|
23
|
8
|
Reasons for withdrawal
| Measure |
Patients With NAFLD
Subjects with biopsy-proven NAFLD; subjects will be challenged with a fructose infusion after a period for 12 hours fasting.
intravenous fructose challenge: Patients will be admitted to our Duke Clinical Research Unit (DCRU) at least 12 hours prior to morning intravenous fructose challenge. All patients will have a "standard" meal in order to control for dietary composition and calorie intake prior to intravenous fructose challenge. Patients will be NPO (nothing by mouth) after midnight for morning IV fructose MR biomarker measures. Patients with suspected NAFLD will have had an historical standard of care liver biopsy in the past and will have IV fructose Magnetic Resonance biomarker measures in the morning.
Blood Draw: Fasting bloodwork will be obtained before and after the IV fructose challenge.
|
Healthy Controls
Healthy controls for comparison with NAFLD patients.The 15 subjects will be challenged with a fructose infusion after a period for 12 hours fasting.
Intravenous fructose challenge: Patients will be admitted to our Duke Clinical Research Unit (DCRU) at least 12 hours prior to morning intravenous fructose challenge. All patients will have a "standard" meal in order to control for dietary composition and calorie intake prior to intravenous fructose challenge. Patients will be NPO (nothing by mouth) after midnight for morning IV fructose MR biomarker measures. Patients with suspected NAFLD will have had an historical standard of care liver biopsy in the past and will have IV fructose Magnetic Resonance biomarker measures in the morning.
Blood Draw: Fasting bloodwork will be obtained before and after the IV fructose challenge.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Physician Decision
|
21
|
8
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Impact of Fructose on Metabolism, Energy Homeostasis and Magnetic Resonance Biomarkers in Nonalcoholic Fatty Liver Disease
Baseline characteristics by cohort
| Measure |
Patients With NAFLD
n=58 Participants
70 subjects with biopsy-proven NAFLD; subjects will be challenged with a fructose infusion after a period for 12 hours fasting.
intravenous fructose challenge: Patients will be admitted to our Duke Clinical Research Unit (DCRU) at least 12 hours prior to morning intravenous fructose challenge. All patients will have a "standard" meal in order to control for dietary composition and calorie intake prior to intravenous fructose challenge. Patients will be NPO (nothing by mouth) after midnight for morning IV fructose MR biomarker measures. Patients with suspected NAFLD will have had an historical standard of care liver biopsy in the past and will have IV fructose Magnetic Resonance biomarker measures in the morning.
Blood Draw: Fasting bloodwork will be obtained before and after the IV fructose challenge.
|
Healthy Controls
n=29 Participants
15 healthy controls for comparison with NAFLD patients.The 15 subjects will be challenged with a fructose infusion after a period for 12 hours fasting.
intravenous fructose challenge: Patients will be admitted to our Duke Clinical Research Unit (DCRU) at least 12 hours prior to morning intravenous fructose challenge. All patients will have a "standard" meal in order to control for dietary composition and calorie intake prior to intravenous fructose challenge. Patients will be NPO (nothing by mouth) after midnight for morning IV fructose MR biomarker measures. Patients with suspected NAFLD will have had an historical standard of care liver biopsy in the past and will have IV fructose Magnetic Resonance biomarker measures in the morning.
Blood Draw: Fasting bloodwork will be obtained before and after the IV fructose challenge.
|
Total
n=87 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53.0 years
STANDARD_DEVIATION 10.2 • n=5 Participants
|
38.0 years
STANDARD_DEVIATION 16.9 • n=7 Participants
|
48.0 years
STANDARD_DEVIATION 13.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
39 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
56 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
84 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
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
47 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
69 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (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 States
|
58 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to approximately one hour post-fructose administrationPopulation: Not applicable to the Patients with NAFLD arm. Data collected on 19 healthy controls.
Outcome measures
| Measure |
Patients With NAFLD
Subjects with biopsy-proven NAFLD; subjects will be challenged with a fructose infusion after a period for 12 hours fasting.
intravenous fructose challenge: Patients will be admitted to our Duke Clinical Research Unit (DCRU) at least 12 hours prior to morning intravenous fructose challenge. All patients will have a "standard" meal in order to control for dietary composition and calorie intake prior to intravenous fructose challenge. Patients will be NPO (nothing by mouth) after midnight for morning IV fructose MR biomarker measures. Patients with suspected NAFLD will have had an historical standard of care liver biopsy in the past and will have IV fructose Magnetic Resonance biomarker measures in the morning.
Blood Draw: Fasting bloodwork will be obtained before and after the IV fructose challenge.
|
Healthy Controls
n=19 Participants
Healthy controls for comparison with NAFLD patients. The subjects will be challenged with a fructose infusion after a period for 12 hours fasting.
intravenous fructose challenge: Patients will be admitted to our Duke Clinical Research Unit (DCRU) at least 12 hours prior to morning intravenous fructose challenge. All patients will have a "standard" meal in order to control for dietary composition and calorie intake prior to intravenous fructose challenge. Patients will be NPO (nothing by mouth) after midnight for morning IV fructose MR biomarker measures. Patients with suspected NAFLD will have had an historical standard of care liver biopsy in the past and will have IV fructose Magnetic Resonance biomarker measures in the morning.
Blood Draw: Fasting bloodwork will be obtained before and after the IV fructose challenge.
|
|---|---|---|
|
Change in Blood Glucose Level From Pre-fructose Administration to Post-fructose Administration in Control Cohort
|
—
|
6.26 mg/dL
Standard Deviation 9.98
|
PRIMARY outcome
Timeframe: Baseline to approximately one hour post-fructose administrationPopulation: Participants with mild or advanced fibrosis. Not applicable to the healthy controls arm.
Comparison between participants with mild fibrosis and participants with advanced fibrosis per the NAFLD Fibrosis score. The NAFLD Fibrosis score is a non-invasive scoring system based on several laboratory tests that helps to estimate the amount of scarring in the liver. A score of F0 or F1 is considered mild, F2 is indeterminate, and F3 or F4 is considered advanced.
Outcome measures
| Measure |
Patients With NAFLD
n=33 Participants
Subjects with biopsy-proven NAFLD; subjects will be challenged with a fructose infusion after a period for 12 hours fasting.
intravenous fructose challenge: Patients will be admitted to our Duke Clinical Research Unit (DCRU) at least 12 hours prior to morning intravenous fructose challenge. All patients will have a "standard" meal in order to control for dietary composition and calorie intake prior to intravenous fructose challenge. Patients will be NPO (nothing by mouth) after midnight for morning IV fructose MR biomarker measures. Patients with suspected NAFLD will have had an historical standard of care liver biopsy in the past and will have IV fructose Magnetic Resonance biomarker measures in the morning.
Blood Draw: Fasting bloodwork will be obtained before and after the IV fructose challenge.
|
Healthy Controls
Healthy controls for comparison with NAFLD patients. The subjects will be challenged with a fructose infusion after a period for 12 hours fasting.
intravenous fructose challenge: Patients will be admitted to our Duke Clinical Research Unit (DCRU) at least 12 hours prior to morning intravenous fructose challenge. All patients will have a "standard" meal in order to control for dietary composition and calorie intake prior to intravenous fructose challenge. Patients will be NPO (nothing by mouth) after midnight for morning IV fructose MR biomarker measures. Patients with suspected NAFLD will have had an historical standard of care liver biopsy in the past and will have IV fructose Magnetic Resonance biomarker measures in the morning.
Blood Draw: Fasting bloodwork will be obtained before and after the IV fructose challenge.
|
|---|---|---|
|
Fructose-induced Change in Low Density Lipoproteins (LDL) Level
NAFLD mild fibrosis
|
5.47 mg/dL
Standard Deviation 6.4
|
—
|
|
Fructose-induced Change in Low Density Lipoproteins (LDL) Level
NAFLD advanced fibrosis
|
-1.13 mg/dL
Standard Deviation 6.85
|
—
|
SECONDARY outcome
Timeframe: 6 Baseline measurements (~3 min), fructose injection and then approximately 30-50 minutes of 31P MRS with scans at 90 secondsPopulation: Participants who had sufficient quality of MRS data.
Percent change of beta-ATP from baseline levels to lowest level (nadir) were evaluated in both controls and NAFLD subjects. 31P-MRS (magnetic resonance spectroscopy) measurements made every 90 seconds.
Outcome measures
| Measure |
Patients With NAFLD
n=30 Participants
Subjects with biopsy-proven NAFLD; subjects will be challenged with a fructose infusion after a period for 12 hours fasting.
intravenous fructose challenge: Patients will be admitted to our Duke Clinical Research Unit (DCRU) at least 12 hours prior to morning intravenous fructose challenge. All patients will have a "standard" meal in order to control for dietary composition and calorie intake prior to intravenous fructose challenge. Patients will be NPO (nothing by mouth) after midnight for morning IV fructose MR biomarker measures. Patients with suspected NAFLD will have had an historical standard of care liver biopsy in the past and will have IV fructose Magnetic Resonance biomarker measures in the morning.
Blood Draw: Fasting bloodwork will be obtained before and after the IV fructose challenge.
|
Healthy Controls
n=10 Participants
Healthy controls for comparison with NAFLD patients. The subjects will be challenged with a fructose infusion after a period for 12 hours fasting.
intravenous fructose challenge: Patients will be admitted to our Duke Clinical Research Unit (DCRU) at least 12 hours prior to morning intravenous fructose challenge. All patients will have a "standard" meal in order to control for dietary composition and calorie intake prior to intravenous fructose challenge. Patients will be NPO (nothing by mouth) after midnight for morning IV fructose MR biomarker measures. Patients with suspected NAFLD will have had an historical standard of care liver biopsy in the past and will have IV fructose Magnetic Resonance biomarker measures in the morning.
Blood Draw: Fasting bloodwork will be obtained before and after the IV fructose challenge.
|
|---|---|---|
|
Dynamic 31P Changes in Liver Beta-ATP Due to Fructose Injection
|
56.7 percentage of change
Standard Deviation 2.6
|
47.9 percentage of change
Standard Deviation 5.2
|
Adverse Events
Patients With NAFLD
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Healthy Controls
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Patients With NAFLD
n=81 participants at risk
Subjects with biopsy-proven NAFLD; subjects will be challenged with a fructose infusion after a period for 12 hours fasting.
intravenous fructose challenge: Patients will be admitted to our Duke Clinical Research Unit (DCRU) at least 12 hours prior to morning intravenous fructose challenge. All patients will have a "standard" meal in order to control for dietary composition and calorie intake prior to intravenous fructose challenge. Patients will be NPO (nothing by mouth) after midnight for morning IV fructose MR biomarker measures. Patients with suspected NAFLD will have had an historical standard of care liver biopsy in the past and will have IV fructose Magnetic Resonance biomarker measures in the morning.
Blood Draw: Fasting bloodwork will be obtained before and after the IV fructose challenge.
|
Healthy Controls
n=37 participants at risk
Healthy controls for comparison with NAFLD patients. The subjects will be challenged with a fructose infusion after a period for 12 hours fasting.
intravenous fructose challenge: Patients will be admitted to our Duke Clinical Research Unit (DCRU) at least 12 hours prior to morning intravenous fructose challenge. All patients will have a "standard" meal in order to control for dietary composition and calorie intake prior to intravenous fructose challenge. Patients will be NPO (nothing by mouth) after midnight for morning IV fructose MR biomarker measures. Patients with suspected NAFLD will have had an historical standard of care liver biopsy in the past and will have IV fructose Magnetic Resonance biomarker measures in the morning.
Blood Draw: Fasting bloodwork will be obtained before and after the IV fructose challenge.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Swelling
|
1.2%
1/81 • up to 24 hours
|
0.00%
0/37 • up to 24 hours
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place