NAFLDISGUNCT04938544
Determination of Insulin-stimulated Hepatic Glucose Uptake by PET-CT Measurements
An observational study of NAFLD and Insulin Resistance, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
In the absence of excessive alcohol consumption, increased levels of fat in the liver (>5%) are diagnosed as non-alcoholic fatty liver (NAFL). It has been shown that NAFL is strongly associated with impairments in metabolic health such as hepatic and whole-body insulin resistance. Read more about this study
- Who is it for?
- Ages 45 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- NAFLD, Insulin Resistance, Overweight and Obesity
- How many people
- 15 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Aug 2021to 31 May 2023
- Phase
- Observational
- 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 45 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: A total of 15 healthy overweight/obese males and post-menopausal females (45-75 years, BMI 27-38 kg/m2) will participate in the study. Recruitment of participants will be performed in Maastricht and surroundings, by means of posters in public spaces (supermarkets, hospital, pharmacy, general practitioners), advertisements in local newspapers (e.g. Dagblad de Limburger and EenLokaal) and on the internet (e.g. digiprik.nl, proefbunny.nl and facebook.nl). Participants from previous studies will be contacted as well in case they provided written consent for this. To increase recruitment efficiency, potential participants can register at a mailing list. With this list, the researcher can approach individuals who showed interest in participating scientific research.
Who may be able to join
- Caucasian (people will be excluded when having a ≥50% racial African/Asian background)
- Male or postmenopausal female
- Aged 45-75 years at start of the study
- Body mass index (BMI) 27 - 38 kg/m2
- Stable dietary habits (no weight loss or gain >3kg in the past 3 months)
- Sedentary lifestyle (not more than 2 hours of vigorous exercise per week)
Who cannot join
- Type 2 diabetes (fasted blood glucose > 7 mmol/L)
- Any condition or medical history that would in the investigator's or dependent physician's opinion interfere with the study, with study outcomes or increase the risk of the study procedures
- Alcohol consumption of >2 servings per day
- Smoking
- Low Hb (men: <8.6 mmol/L; women <7.4 mmol/L)
- Use of medication known to interfere with the safety of study procedures
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- Use of medication known to increase liver fat, like for instance corticosteroids (parenteral \& oral chronic administration only), amiodarone (Cordarone), tamoxifen (Nolvadex), and methotrexate (Rheumatrex, Trexall).
- Subjects receiving thiazolidinediones (glitazones [pioglitazone, rosiglitazone]).
- Participation in research or medical examination that included PET/CT scanning in the last 3 months
- Contra-indication for MRI
Trial locations and contacts
1 site in 1 country.
Vera Schrauwen-Hinderling, PhD contact
Netherlands1 site, 1 recruiting
- Recruiting
Maastricht University
Maastricht, 6229 ER
Jeremy Basset Sagarminaga, MSc, 0031638145779, j.bassetsagarminaga@maastrichtuniversity.nl
Kay Roumans, MSc, 0031433882124, k.roumans@maastrichtuniversity.nl
About this study
In the absence of excessive alcohol consumption, increased levels of fat in the liver (>5%) are diagnosed as non-alcoholic fatty liver (NAFL). It has been shown that NAFL is strongly associated with impairments in metabolic health such as hepatic and whole-body insulin resistance. Insulin resistance is seen as the earliest hallmark in the development of type 2 diabetes.
Insulin has two main effects on the liver: suppressing endogenous glucose production (EGP) and increasing glucose uptake. While the former has been extensively studied and is known to be impaired in NAFL, no studies have yet examined whether insulin-stimulated hepatic glucose uptake is affected by NAFL.
Read more
Recent methodological developments allow us to visualize and quantify glucose uptake in any given tissue using dynamic Positron Emission Tomography (PET) with 18Fluorinated glucose tracer (FDG) during insulin stimulation.
In the present study, we will in a first instance optimize the insulin-stimulated whole-body PET protocol and apply the dose as reported in the literature 4 megabequerels per kg of body weight (MBq/kg) (±8 mSv) in the first three subjects. It will then be evaluated whether the dose can be decreased in the remaining measurements. Another twelve individuals will then undergo the optimized dynamic PET protocol to assess insulin-stimulated hepatic glucose together with whole-body glucose uptake measures. Liver fat content and composition will be assessed by proton magnetic resonance spectroscopy (1H-MRS). Fasted De Novo Lipogenesis (DNL) will also be measured by deuterated water. Additionally, a two-step clamp will be performed to measure whole-body insulin sensitivity and insulin-stimulated suppression of EGP. The identification of the contributing factors to insulin resistance during the development of NAFL is crucial in order to develop more effective strategies for the prevention and treatment of metabolic disorders.
Read the detailed description
Objective:
To determine the association between insulin-stimulated hepatic glucose uptake measured by dynamic PET and liver fat content in overweight/obese subjects.
- Conditions
- NAFLD, Insulin Resistance, Overweight and Obesity
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Insulin Resistance, Overweight, Obesity
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin-stimulated glucose uptake measured by PET-CT measured by dynamic [18F]-FDG PET
Insulin-stimulated hepatic glucose uptake rate constant (Ki) will be determined by [18F]- FDG PET, by using the Patlak method (Patlak et al. 1983) in each voxel. Influx rate will be calculated in mL/cm3/min
Measured: 1 hour
Hepatic fat content by 1H-MRS
Liver fat will be quantified by 1H-MRS with which the water and fat resonances can be detected. The intensity of the fat resonance will be expressed relative to the water resonance (%).
Measured: 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2021
- Study start1 Aug 2021
- Primary completion31 May 2023 (estimated)
- Study completion31 May 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NAFLDStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vera Schrauwen-Hinderling, PhD, Principal investigator, v.schrauwen@maastrichtuniversity.nl
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04938544
- Sponsor's protocol ID
- NL74609.068.20
- Acronym
- ISGU
- Status last verified
- Mar 2023
- First submitted
- 8 Jun 2021
- Last updated
- 29 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determination of Insulin-stimulated Hepatic Glucose Uptake by PET-CT Measurements
- ClinicalTrials.gov ID
- NCT04938544
- Acronym / sponsor ID
- ISGU / NL74609.068.20
- Conditions
- NAFLD, Insulin Resistance, Overweight and Obesity
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- 1 Aug 2021 (actual)
- Primary completion
- 31 May 2023 (estimated)
- Study completion
- 31 May 2023 (estimated)
- First posted
- 24 Jun 2021 (actual)
- 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.
In the absence of excessive alcohol consumption, increased levels of fat in the liver (>5%) are diagnosed as non-alcoholic fatty liver (NAFL). It has been shown that NAFL is strongly associated with impairments in metabolic health such as hepatic and whole-body insulin resistance. Insulin resistance is seen as the earliest hallmark in the development of type 2 diabetes.
Insulin has two main effects on the liver: suppressing endogenous glucose production (EGP) and increasing glucose uptake. While the former has been extensively studied and is known to be impaired in NAFL, no studies have yet examined whether insulin-stimulated hepatic glucose uptake is affected by NAFL.
Recent methodological developments allow us to visualize and quantify glucose uptake in any given tissue using dynamic Positron Emission Tomography (PET) with 18Fluorinated glucose tracer (FDG) during insulin stimulation.
In the present study, we will in a first instance optimize the insulin-stimulated whole-body PET protocol and apply the dose as reported in the literature 4 megabequerels per kg of body weight (MBq/kg) (±8 mSv) in the first three subjects. It will then be evaluated whether the dose can be decreased in the remaining measurements. Another twelve individuals will then undergo the optimized dynamic PET protocol to assess insulin-stimulated hepatic glucose together with whole-body glucose uptake measures. Liver fat content and composition will be assessed by proton magnetic resonance spectroscopy (1H-MRS). Fasted De Novo Lipogenesis (DNL) will also be measured by deuterated water. Additionally, a two-step clamp will be performed to measure whole-body insulin sensitivity and insulin-stimulated suppression of EGP. The identification of the contributing factors to insulin resistance during the development of NAFL is crucial in order to develop more effective strategies for the prevention and treatment of metabolic disorders.
Detailed description
Objective:
To determine the association between insulin-stimulated hepatic glucose uptake measured by dynamic PET and liver fat content in overweight/obese subjects.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- A total of 15 healthy overweight/obese males and post-menopausal females (45-75 years, BMI 27-38 kg/m2) will participate in the study. Recruitment of participants will be performed in Maastricht and surroundings, by means of posters in public spaces (supermarkets, hospital, pharmacy, general practitioners), advertisements in local newspapers (e.g. Dagblad de Limburger and EenLokaal) and on the internet (e.g. digiprik.nl, proefbunny.nl and facebook.nl). Participants from previous studies will be contacted as well in case they provided written consent for this. To increase recruitment efficiency, potential participants can register at a mailing list. With this list, the researcher can approach individuals who showed interest in participating scientific research.
Key inclusion criteria (6 listed)
- Caucasian (people will be excluded when having a ≥50% racial African/Asian background)
- Male or postmenopausal female
- Aged 45-75 years at start of the study
- Body mass index (BMI) 27 - 38 kg/m2
- Stable dietary habits (no weight loss or gain >3kg in the past 3 months)
Key exclusion criteria (10 listed)
- Type 2 diabetes (fasted blood glucose > 7 mmol/L)
- Any condition or medical history that would in the investigator's or dependent physician's opinion interfere with the study, with study outcomes or increase the risk of the study procedures
- Alcohol consumption of >2 servings per day
- Smoking
- Low Hb (men: <8.6 mmol/L; women <7.4 mmol/L)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Insulin-stimulated glucose uptake measured by PET-CT measured by dynamic [18F]-FDG PET
Time frame: 1 hour
Insulin-stimulated hepatic glucose uptake rate constant (Ki) will be determined by [18F]- FDG PET, by using the Patlak method (Patlak et al. 1983) in each voxel. Influx rate will be calculated in mL/cm3/min
Hepatic fat content by 1H-MRS
Time frame: 1 hour
Liver fat will be quantified by 1H-MRS with which the water and fat resonances can be detected. The intensity of the fat resonance will be expressed relative to the water resonance (%).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2023.
- Individual participant dataSharing planned: Undecided
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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.
Vera Schrauwen-Hinderling, PhD contact
Vera Schrauwen-Hinderling, PhD principal investigator
v.schrauwen@maastrichtuniversity.nl
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of NAFLD and Insulin Resistance, run by Maastricht University Medical Center at 1 site in Netherlands.
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 6 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 29 Mar 2023. 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 Netherlands. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jeremy B Sagarminaga, MSc (0638145779, jeremy.basset.s@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin-stimulated glucose uptake measured by PET-CT measured by dynamic [18F]-FDG PET (time frame: 1 hour). The study lists 2 primary outcomes in all. 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 29 Mar 2023.