ObesityEarly Phase 1NCT01807910
ER Stress in NAFLD
A Early Phase 1 study testing methyl-D9-choline in people with Obesity and NAFLD, run by Vanderbilt University at 1 site in United States.
Trial summary
The investigators overall hypothesis is that exacerbation of endoplasmic reticulum (ER) stress in the liver is associated with significant alterations in phosphatidylcholines that drive the NASH phenotype in obese humans. Read more about this study
- Who is it for?
- Ages 30 to 60 years, women only
- What is being tested?
- methyl-D9-choline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to Apr 2018
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 60 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Ambulatory females age 30-60 years old
- Women of all ethnic groups
- BMI≥35 kg/m2
- Approval for Roux-en-Y gastric bypass or sleeve gastrectomy.
Who cannot join
- Smoking >7 cigarettes per day
- Previous malabsorptive or restrictive intestinal surgery
- Pregnant or breastfeeding
- Recent history of neoplasia (<5 years ago)
- Malabsorptive syndromes
- Inflammatory intestinal disease
Show all 14Show fewer
- Patients with established organ dysfunction
- Diagnosis of type 1 or type 2 diabetes mellitus or current use of anti-diabetic medication (last 30 days; last 60days for thiazolidinediones)
- Diagnosed hyperbetalipoproteinemia or hypobetalipoproteinemia
- Patients on cholesterol lowering medicines
- Vegan diet
- Hepatic fat content <10% by MRI
- Inability to comply with study protocol such as unable to make study visits or be available daily for phone contact
- Any condition which would interfere with MRI or PET studies, e.g. claustrophobia, cochlear implant, chronic back pain limiting ability to lay flat, metal fragments in eyes, cardiac pacemaker, neural stimulator, tattoos with iron pigment and metallic body inclusions or other metal implanted in the body which may interfere with MRI scanning.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: Phospholipid Endoplasmic Reticulum Stress in Nonalcoholic Fatty Liver Disease
The investigators overall hypothesis is that exacerbation of endoplasmic reticulum (ER) stress in the liver is associated with significant alterations in phosphatidylcholines that drive the NASH phenotype in obese humans. The investigators plan to examine this hypothesis in a well-characterized cohort of obese subjects that are scheduled for bariatric surgery. Methyl-D9-choline chloride will be infused before and after a 2-week high fructose or glucose feeding to determine the biosynthesis and kinetics of secretory lipoprotein phospholipids. It is proposed that phospholipid metabolism play an important role in the pathogenesis or etiology of fatty liver in non-alcoholic conditions through mechanisms that invoke ER and oxidative stress responses.
- Being tested
- methyl-D9-choline
- Keywords
- Obesity, NAFLD, NASH, Steatosis
- Medical subject headings
- Obesity, Non-alcoholic Fatty Liver Disease, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
methyl-D9-cholineDrug
Subjects in both arms will be infused with methyl-D9-choline in order to assess the biosynthesis and kinetics of secretory lipoprotein phospholipids.
| Study group | Role | What they receive |
|---|---|---|
| Fructose | Experimental | Participants will receive fructose (3g/kg/day) for 2 weeks. Receives: Drug: methyl-D9-choline |
| Glucose | Active comparator | Participants will receive glucose (3g/kg/day) for 2 weeks. Receives: Drug: methyl-D9-choline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Net hepatic phospholipid production
Net hepatic phospholipid production will be determined using [11C]choline dynamic Positron Emission Tomography (PET) before and after high fructose feeding for two weeks. A similar group of control obese subjects will undergo the same procedures before and after two weeks isocaloric glucose feeding.
Measured: Baseline and 2 weeks
Secondary outcomes (1)
Kinetics of secretory lipoprotein phospholipids
The biosynthesis and kinetics of secretory lipoprotein phospholipids will be determined using methyl-D9-choline chloride infusion before and after high fructose (or glucose) feeding.
Measured: Baseline and 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2013 (estimated)
- Study startOct 2013
- Primary completionOct 2017 (estimated)
- Study completionApr 2018 (estimated)
Why it stopped: The study was not funded
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Charles R. Flynn, Vanderbilt University
- Investigators
- Charles R Flynn, PhD, Principal investigator, Vanderbilt University Medical CenterNaji N Abumrad, MD, Study chair, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01807910
- Sponsor's protocol ID
- ER stress
- Status last verified
- Oct 2013
- First submitted
- 5 Mar 2013
- Last updated
- 23 Oct 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phospholipid Endoplasmic Reticulum Stress in Nonalcoholic Fatty Liver Disease
- ClinicalTrials.gov ID
- NCT01807910
- Acronym / sponsor ID
- ER stress
- Keywords
- Obesity, NAFLD, NASH, Steatosis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study was not funded
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Oct 2017 (estimated)
- Study completion
- Apr 2018 (estimated)
- First posted
- 8 Mar 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators overall hypothesis is that exacerbation of endoplasmic reticulum (ER) stress in the liver is associated with significant alterations in phosphatidylcholines that drive the NASH phenotype in obese humans. The investigators plan to examine this hypothesis in a well-characterized cohort of obese subjects that are scheduled for bariatric surgery. Methyl-D9-choline chloride will be infused before and after a 2-week high fructose or glucose feeding to determine the biosynthesis and kinetics of secretory lipoprotein phospholipids. It is proposed that phospholipid metabolism play an important role in the pathogenesis or etiology of fatty liver in non-alcoholic conditions through mechanisms that invoke ER and oxidative stress responses.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fructose | Experimental | Drug: methyl-D9-cholineParticipants will receive fructose (3g/kg/day) for 2 weeks. |
| Glucose | Active comparator | Drug: methyl-D9-cholineParticipants will receive glucose (3g/kg/day) for 2 weeks. |
Who may qualify
- Ages
- 30 to 60 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Ambulatory females age 30-60 years old
- Women of all ethnic groups
- BMI≥35 kg/m2
- Approval for Roux-en-Y gastric bypass or sleeve gastrectomy.
Key exclusion criteria (14 listed)
- Smoking >7 cigarettes per day
- Previous malabsorptive or restrictive intestinal surgery
- Pregnant or breastfeeding
- Recent history of neoplasia (<5 years ago)
- Malabsorptive syndromes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| methyl-D9-cholineSubjects in both arms will be infused with methyl-D9-choline in order to assess the biosynthesis and kinetics of secretory lipoprotein phospholipids. | Drug | Fructose, Glucose |
Primary outcome
Net hepatic phospholipid production
Time frame: Baseline and 2 weeks
Net hepatic phospholipid production will be determined using [11C]choline dynamic Positron Emission Tomography (PET) before and after high fructose feeding for two weeks. A similar group of control obese subjects will undergo the same procedures before and after two weeks isocaloric glucose feeding.
1 secondary outcome
Kinetics of secretory lipoprotein phospholipids
Time frame: Baseline and 2 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles R Flynn, PhD principal investigator
Vanderbilt University Medical Center
Naji N Abumrad, MD study chair
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing methyl-D9-choline in people with Obesity and NAFLD, run by Vanderbilt University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 23 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Net hepatic phospholipid production (time frame: Baseline and 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2013.