Back to resultsSafety and Efficacy of Ketogenic Diet for Promoting Weight Loss in Obese Individuals With Compensated NASH Cirrhosis
Primary Purpose
NASH - Nonalcoholic Steatohepatitis, Cirrhosis, Liver
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Dietary consult for participants in the ketogenic diet arm
Dietary consult for participants in the standard of care arm
Sponsored by
About this trial
This is an interventional treatment trial for NASH - Nonalcoholic Steatohepatitis
Eligibility Criteria
Inclusion Criteria:
- NASH cirrhosis (criteria in Appendix 1) with obesity (BMI >30 kg/m2).
- Age 18 and greater
Exclusion Criteria:
- Actively participation in investigational drug treatment for non-alcoholic fatty liver disease
- Currently taking medications for weight loss or have joined a supervised weight loss program prior to enrollment
- Have hepatocellular carcinoma and are undergoing therapy
- Women who become pregnant or plan to become pregnant prior to the study date; female subjects who become pregnant during the study will be withdrawn from the study
- Pacemaker or implantable cardioverter devices
- History of hepatic surgery
- Current significant alcohol consumption, defined as more than 20 grams per day in females or 30 grams per day in males
- Presence of ascites or hepatic encephalopathy
- Symptomatic gastroparesis
- Uncontrolled diabetes, as defined by a HgbA1C >11%
- Uncontrolled congestive heart failure
- Active infections
- Child Turcotte Pugh score > 6
- MELD score >12
- Unwilling to undergo an MRI or have contraindications to an MRI
Sites / Locations
- Indiana University School of MedicineRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Sham Comparator
Arm Label
Ketogenic diet
Standard of Care
Arm Description
For participants randomized to the ketogenic diet arm, a consultation with the providers of medically supervised weight loss clinic of Indiana University Health will be arranged. Subjects will be educated on the concepts of ketosis, symptoms associated with it, and dietary manipulation to achieve ketosis. Participants in this arm will use the suggested recipes in combination with strict carbohydrate monitoring though checking for urine ketone bodies. These recipes were gathered and vetted by the dietitian at the medically supervised weight loss clinic. We anticipate that this approach will allow for more calorie intake and easier carbohydrate restriction. The follow up visits will be determined by the providers of the medically supervised weight loss clinic based on the symptoms reported and subject's compliance with carbohydrate restriction.
For participants randomized to this arm, a consultation with the providers of medically supervised weight loss clinic will be arranged. The discussion will focus on portion control using a balanced diet. A follow up visit will be at 16 weeks. This is the extent of interventions received for participants in this arm.
Outcomes
Primary Outcome Measures
Blood chemistry to assess for liver de-compensation events
Blood will be drawn serially to assess fasting blood glucose, serum creatinine and fasting lipid profile.
Blood chemistry to assess for liver de-compensation events
Blood will be drawn serially to assess fasting blood glucose, serum creatinine and fasting lipid profile.
Blood chemistry to assess for liver de-compensation events
Blood will be drawn serially to assess fasting blood glucose, serum creatinine and fasting lipid profile.
Adverse events
All participants will be monitored for adverse events and/or serious adverse events throughout the duration of the trial.
Adverse events
All participants will be monitored for adverse events and/or serious adverse events throughout the duration of the trial.
Tolerability of the ketogenic diet
How well the ketogenic diets is tolerated will be assessed by administering a POMS40 questionnaire.
Tolerability of the ketogenic diet
How well the ketogenic diets is tolerated will be assessed by administering a POMS40 questionnaire.
Tolerability of the ketogenic diet
How well the ketogenic diets is tolerated will be assessed by administering a POMS40 questionnaire.
Secondary Outcome Measures
MRI with proton density fat fraction (PDFF)
MRI-PDFF is a convenient method for liver fat quantification and currently used in most clinical trials, as it only requires a single 20-second breath hold and an estimated time of about 5 minutes in an MRI scanner suite. MRI in the study will be used to quantify liver steatosis, stiffness, and body composition.
Weight loss and change in body composition
Changes in weight and body composition will be measured via serial use of a scale and use of bioelectrical impedance via an Inbody machine
Changes in liver stiffness and steatosis
Changes in liver stiffness and steatosis will be measured with serial use of vibration controlled transient elastography (VCTE) via a FibroScan.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04383951
Brief Title
Safety and Efficacy of Ketogenic Diet for Promoting Weight Loss in Obese Individuals With Compensated NASH Cirrhosis
Official Title
Safety and Efficacy of Ketogenic Diet for Promoting Weight Loss in Obese Individuals With Compensated NASH Cirrhosis
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 15, 2020 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indiana University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an open-label, randomized study comparing a monitored ketogenic diet intervention using standard ketogenic diet (SKD) and standard of care (SOC) dietary recommendations for 16 weeks. Subjects enrolled in the standard of care group will receive a voucher to Weight Watchers after study completion.
Detailed Description
The primary aim is to assess the safety of ketogenic diet as compared to standard of care approach for weight loss in patients with compensated cirrhosis due to NASH. The safety endpoints captured in the study include liver decompensation events, measured through several questionnaires, fasting blood glucose, serum creatinine, fasting lipid profile and other adverse events. The tolerability of the ketogenic diet will be assessed by study compliance and by administering a questionnaire.
Secondary aims include weight loss, changes in body composition via serial use of bioelectrical impedance via an Inbody Machine, changes in liver fat and liver stiffness using MRI and proton density fat fraction (MRI-PDFF), liver biochemistries, changes in Child-Turcotte-Pugh and MELD scores measured via labs and changes in liver steatosis and stiffness via serial measures of VCTE by FibroScan®.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NASH - Nonalcoholic Steatohepatitis, Cirrhosis, Liver
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Block randomization will be utilized to ensure balancing of treatment groups throughout enrollment. 30 participants will be assigned to the ketogenic diet arm and 10 will be assigned to standard of care.
Masking
Investigator
Masking Description
While this is an open label study, the principal investigator will be blinded to the results of efficacy outcomes such as MRI-PDFF, Body composition data, VCTE by FibroScan® and study questionnaires.
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Ketogenic diet
Arm Type
Active Comparator
Arm Description
For participants randomized to the ketogenic diet arm, a consultation with the providers of medically supervised weight loss clinic of Indiana University Health will be arranged. Subjects will be educated on the concepts of ketosis, symptoms associated with it, and dietary manipulation to achieve ketosis. Participants in this arm will use the suggested recipes in combination with strict carbohydrate monitoring though checking for urine ketone bodies. These recipes were gathered and vetted by the dietitian at the medically supervised weight loss clinic. We anticipate that this approach will allow for more calorie intake and easier carbohydrate restriction. The follow up visits will be determined by the providers of the medically supervised weight loss clinic based on the symptoms reported and subject's compliance with carbohydrate restriction.
Arm Title
Standard of Care
Arm Type
Sham Comparator
Arm Description
For participants randomized to this arm, a consultation with the providers of medically supervised weight loss clinic will be arranged. The discussion will focus on portion control using a balanced diet. A follow up visit will be at 16 weeks. This is the extent of interventions received for participants in this arm.
Intervention Type
Other
Intervention Name(s)
Dietary consult for participants in the ketogenic diet arm
Intervention Description
An initial consultation with the providers of medically supervised weight loss clinic will be arranged. Participants in the ketogenic diet group will be educated on the concepts of the diet and will be provided with recipes to be utilized at home that adhere to this diet. In addition to the initial consultation, participants in this arm receive additional consultations with these providers with a frequency as determined by the provider.
Intervention Type
Other
Intervention Name(s)
Dietary consult for participants in the standard of care arm
Intervention Description
For participants in the standard of care arm, an initial consultation with the providers of medically supervised weight loss clinic will be arranged and the discussion will center around portion control using a balanced diet. Participants will receive only one additional consultation with the provider 16 weeks later just prior to the conclusion of the study.
Primary Outcome Measure Information:
Title
Blood chemistry to assess for liver de-compensation events
Description
Blood will be drawn serially to assess fasting blood glucose, serum creatinine and fasting lipid profile.
Time Frame
Blood chemistry tests will be assessed at the initial visit.
Title
Blood chemistry to assess for liver de-compensation events
Description
Blood will be drawn serially to assess fasting blood glucose, serum creatinine and fasting lipid profile.
Time Frame
Blood chemistry tests will be assessed at the study visits between weeks 5 and 14.
Title
Blood chemistry to assess for liver de-compensation events
Description
Blood will be drawn serially to assess fasting blood glucose, serum creatinine and fasting lipid profile.
Time Frame
Blood chemistry tests will be assessed at the Week 16 visit.
Title
Adverse events
Description
All participants will be monitored for adverse events and/or serious adverse events throughout the duration of the trial.
Time Frame
All participants will be monitored at the study visits between weeks 5 and 14 and all participants will be instructed to alert the study team for additional information if such an event occurs.
Title
Adverse events
Description
All participants will be monitored for adverse events and/or serious adverse events throughout the duration of the trial.
Time Frame
All participants will be monitored at the week 16 visit and all participants will be instructed to alert the study team for additional information if such an event occurs.
Title
Tolerability of the ketogenic diet
Description
How well the ketogenic diets is tolerated will be assessed by administering a POMS40 questionnaire.
Time Frame
The POMS 40 questionnaire is administered at the initial visit.
Title
Tolerability of the ketogenic diet
Description
How well the ketogenic diets is tolerated will be assessed by administering a POMS40 questionnaire.
Time Frame
The POMS 40 questionnaire is administered at the study visits between weeks 1 and 4.
Title
Tolerability of the ketogenic diet
Description
How well the ketogenic diets is tolerated will be assessed by administering a POMS40 questionnaire.
Time Frame
The POMS 40 questionnaire is administered at the Week 16 visit.
Secondary Outcome Measure Information:
Title
MRI with proton density fat fraction (PDFF)
Description
MRI-PDFF is a convenient method for liver fat quantification and currently used in most clinical trials, as it only requires a single 20-second breath hold and an estimated time of about 5 minutes in an MRI scanner suite. MRI in the study will be used to quantify liver steatosis, stiffness, and body composition.
Time Frame
Performed at initial visit and at week 16 visit
Title
Weight loss and change in body composition
Description
Changes in weight and body composition will be measured via serial use of a scale and use of bioelectrical impedance via an Inbody machine
Time Frame
Performed at initial visit and at week 16 visit
Title
Changes in liver stiffness and steatosis
Description
Changes in liver stiffness and steatosis will be measured with serial use of vibration controlled transient elastography (VCTE) via a FibroScan.
Time Frame
Performed at initial visit and at week 16 visit
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
NASH cirrhosis (criteria in Appendix 1) with obesity (BMI >30 kg/m2).
Age 18 and greater
Exclusion Criteria:
Actively participation in investigational drug treatment for non-alcoholic fatty liver disease
Currently taking medications for weight loss or have joined a supervised weight loss program prior to enrollment
Have hepatocellular carcinoma and are undergoing therapy
Women who become pregnant or plan to become pregnant prior to the study date; female subjects who become pregnant during the study will be withdrawn from the study
Pacemaker or implantable cardioverter devices
History of hepatic surgery
Current significant alcohol consumption, defined as more than 20 grams per day in females or 30 grams per day in males
Presence of ascites or hepatic encephalopathy
Symptomatic gastroparesis
Uncontrolled diabetes, as defined by a HgbA1C >11%
Uncontrolled congestive heart failure
Active infections
Child Turcotte Pugh score > 6
MELD score >12
Unwilling to undergo an MRI or have contraindications to an MRI
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Emily Smith, BS
Phone
317-274-1692
Email
es37@iu.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Regina Weber, BS
Phone
317-278-3584
Email
reginaw@iu.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raj Vuppalanchi, M.D.
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indiana University School of Medicine
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Regina Weber, BS
Phone
317-278-3584
Email
reginaw@iu.edu
First Name & Middle Initial & Last Name & Degree
Raj Vuppalanchi, MD
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
No IPD at this time
Learn more about this trial
Safety and Efficacy of Ketogenic Diet for Promoting Weight Loss in Obese Individuals With Compensated NASH Cirrhosis
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