Non-Alcoholic Fatty Liver DiseaseDiaakineNCT06240039
Direct Versus Indirect Effect of Amino Acids on Hepatokines
A study testing Evaluating the acute effect of an amino acid infusion with and without a concomitant infusion of the somatostatin analogue octreotide to eliminate endogenous production of glucagon in people with Non-Alcoholic Fatty Liver Disease and Obesity, run by University of Copenhagen at 1 site in Denmark.
Trial summary
Liver hormones are key metabolic regulators and increased in metabolic diseases, including fatty liver disease. The underlying mechanisms driving the elevated levels are currently unknown and presents a major challenge in understanding the interplay between liver hormones and fatty liver disease. Read more about this study
- Who is it for?
- Ages 25 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Obesity
- What is being tested?
- Evaluating the acute effect of an amino acid infusion with and without a concomitant infusion of the somatostatin analogue octreotide to eliminate endogenous production of glucagon
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteDenmark
- Study dates
- 11 Feb 2024to 1 Sep 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 25 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female between 25-65 years of age at time of screening
- Body mass index of 18.6-25 kg/m2
- Male or female between 25-65 years of age at time of screening
- Body mass index of 25-40 kg/m2
- Hepatic non-alcoholic steatosis verified by liver biopsy, fibroscan or ultrasound
Who cannot join
- Contraindications for MRI-scan
- Severe liver disease (estimated by FIB4 score > 3.25)
- Type 2 diabetes according to ADA criteria
- Significant history of alcoholism or drug/chemical abuse as per investigators judgement
- Amino acid related diseases
- Kidney disease
Show all 25Show fewer
- Cardiac problems
- Cancer within the past 1 year
- Anemia
- Pregnancy or breast feeding
- Smoking
- Any medicine, acute illness (within the last two weeks) or other circumstances that in the opinion of the investigator might endanger the participants' safety or compliance with the protocol
- Group 2 (individuals with hepatic steatosis):
- Contraindications for MRI-scan
- Severe liver disease (estimated by FIB4 score > 3.25)
- Type 2 diabetes according to ADA criteria
- Significant history of alcoholism or drug/chemical abuse as per investigators judgement
- Amino acid related diseases
- Kidney disease
- Cardiac problems
- Cancer within the past 1 year
- Anemia
- Pregnancy or breast feeding
- Smoking
- Any medicine, acute illness (within the last two weeks) or other circumstances that in the opinion of the investigator might endanger the participants' safety or compliance with the protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Direct Versus Indirect Effect of Amino Acids on Hepatokines in Healthy Subjects and Patients With Non-alcoholic Fatty Liver Disease
Liver hormones are key metabolic regulators and increased in metabolic diseases, including fatty liver disease. The underlying mechanisms driving the elevated levels are currently unknown and presents a major challenge in understanding the interplay between liver hormones and fatty liver disease. The project aims to investigate what stimulates the liver to secrete its hormones and why the secretion is increased in patients with fatty liver disease. The investigator (Associate Prof. Nicolai J Wewer Albrechtsen) will investigate the direct and indirect effects of an amino acid amino infusion on the secretion of hepatokines in individuals with and without metabolic dysfunction-associated steatotic liver disease (MASLD).
Read the detailed description
The liver secretes signaling molecules, (termed hepatokines) to the blood circulation which are powerful metabolic regulators and biomarkers of liver disease. Some of the more studied hepatokines include follistatin, fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) and they have been sown to improve glucose tolerance, reduce liver fat content and regulate appetite.
In dysregulated metabolic conditions, including obesity, MASLD and type 2 diabetes, the circulating levels of hepatokines are increased. It could be speculated that the body increases hepatokine levels as a feedback mechanism to combat dysregulated metabolism. However, the underlying mechanisms driving the elevated levels in metabolic disease are currently unknown. The secretion of follistatin, FGF21 and GDF15 from the liver has been suggested to be stimulated by glucagon and amino acids. In dysregulated metabolic diseases, circulating levels of glucagon and amino acids are often increased and are highly dependent on hepatic steatosis. Increased levels of hepatokines observed in dysregulated metabolic individuals could therefore be attributed to an increase in circulating glucagon, amino acids, or a combination of both.
The study aims to explore the direct and indirect effect of amino acids on the regulation of hepatokines in individuals with and without MASLD. The study evaluates the acute effect of an amino acid infusion with and without a concomitant infusion of the somatostatin analogue octreotide to eliminate endogenous production of glucagon, thus isolating the direct effect of amino acids. ,
The investigators hypothesizes that an amino acid infusion will increase the secretion of hepatokines independent of glucagon.
- Conditions
- Non-Alcoholic Fatty Liver Disease, Obesity
- Being tested
- Evaluating the acute effect of an amino acid infusion with and without a concomitant infusion of the somatostatin analogue octreotide to eliminate endogenous production of glucagon
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Evaluating the acute effect of an amino acid infusion with and without a concomitant infusion of the somatostatin analogue octreotide to eliminate endogenous production of glucagonOther
The experimental days consist of four study days:
- Assessment of liver fat and visceral fat by magnetic resonance imaging (MRI; 6-point Dixon) (study day A)
- Somatostatin infusion (4 hours) plus amino acid infusion (45 minutes) (study day B)
- Saline infusion (4 hours) plus amino acid infusion (45 minutes) (study day C)
- Somatostatin infusion (4 hours) plus saline infusion (45 minutes) (study day D)
The subjects will participate in the experimental days (study day B to D) in randomized order on three different days. For study day B to D, at timepoint t = -75, subjects will receive either; a 240-minute intravenous infusion of a somatostatin analogue (at 200 ng/kg/min (infusion rate will not exceed 1000 µg/hour) or saline. After 75 minutes (timepoint t = 0), the subjects will receive a 45-minute intravenous infusion of amino acids or saline at 3.885 ml/kg/hour.
In total, blood will be sampled 11 times over a period of 6 hours and 15 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Evaluating the direct and indirect effect of amino acids on the regulation of hepatokines | Experimental | Participants will be subjected to four experimental days Receives: Other: Evaluating the acute effect of an amino acid infusion with and without a concomitant infusion of the somatostatin analogue octreotide to eliminate endogenous production of glucagon |
What is being measured
The primary outcome is the main question the study is designed to answer.
The direct (amino acid + somatostatin) versus the indirect (amino acid + placebo) effect of amino acids on circulating levels of follistatin.
Defined as the difference in incremental AUC0-300 min (iAUC) of follistatin between study day B and study day C in healthy individuals.
Measured: From blood sample at minute 0 until blood sample at minute 300.
Secondary outcomes (6)
The direct (amino acid + somatostatin) versus the indirect (amino acid + placebo) effect of amino acids on circulating levels of FGF21 and GDF15
Defined as the difference in iAUC0-300 min between study day B and study day C in healthy individuals.
Measured: From blood sample at minute 0 until blood sample at minute 300.
The direct versus the indirect effect of amino acids on circulating levels of hepatokines (follistatin, FGF21 and GDF15).
Defined as the difference in iAUC0-300 min of hepatokines between study day B and study day C in individuals with MASLD.
Measured: From blood sample at minute 0 until blood sample at minute 300
Differences between healthy and MASLD in the increase in hepatokines during study day B (direct effect of amino acids)
Defined as the differences in iAUC0-300 min of hepatokines between healthy and MASLD
Measured: From blood sample at minute 0 until blood sample at minute 300
Differences between healthy and MASLD in the increase in hepatokines during study day C (indirect effect of amino acids).
Defined as the differences in iAUC0-300 min of hepatokines between healthy and MASLD
Measured: From blood sample at minute 0 until blood sample at minute 300
The inhibitory effect of somatostatin versus the stimulatory effect of amino acids on glucagon, insulin and C-peptide levels during study day B in healthy and MASLD.
Defined as the difference between iAUC -75-0 min and iAUC0-45 min in both groups
Measured: From blood sample at minute -75 until blood sample at minute 45
Differences in glucagon, insulin and C-peptide concentrations between study day B and C in healthy and MASLD
Defined as the difference between iAUC0-300 min during study day B and C in healthy and MASLD
Measured: From blood sample at minute 0 until blood sample at minute 300
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2024
- Study start11 Feb 2024
- Primary completion16 Apr 2025
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University of CopenhagenThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Bispebjerg Hospital
- Responsible party
- Principal investigator, Nicolai Jacob Wewer Albrechtsen, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06240039
- Sponsor's protocol ID
- Diaakine
- Acronym
- Diaakine
- Status last verified
- May 2026
- First submitted
- 25 Jan 2024
- Last updated
- 7 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We have not decided to share IPD as this also would require approval from the ethical and data approval committee.
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Direct Versus Indirect Effect of Amino Acids on Hepatokines in Healthy Subjects and Patients With Non-alcoholic Fatty Liver Disease
- ClinicalTrials.gov ID
- NCT06240039
- Acronym / sponsor ID
- Diaakine / Diaakine
- Conditions
- Non-Alcoholic Fatty Liver Disease, Obesity
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of CopenhagenUniversity, hospital or other
- Collaborators
- Bispebjerg Hospital
- Study start
- 11 Feb 2024 (actual)
- Primary completion
- 16 Apr 2025 (actual)
- Study completion
- 1 Sep 2028 (estimated)
- First posted
- 2 Feb 2024 (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.
Liver hormones are key metabolic regulators and increased in metabolic diseases, including fatty liver disease. The underlying mechanisms driving the elevated levels are currently unknown and presents a major challenge in understanding the interplay between liver hormones and fatty liver disease. The project aims to investigate what stimulates the liver to secrete its hormones and why the secretion is increased in patients with fatty liver disease. The investigator (Associate Prof. Nicolai J Wewer Albrechtsen) will investigate the direct and indirect effects of an amino acid amino infusion on the secretion of hepatokines in individuals with and without metabolic dysfunction-associated steatotic liver disease (MASLD).
Detailed description
The liver secretes signaling molecules, (termed hepatokines) to the blood circulation which are powerful metabolic regulators and biomarkers of liver disease. Some of the more studied hepatokines include follistatin, fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) and they have been sown to improve glucose tolerance, reduce liver fat content and regulate appetite.
In dysregulated metabolic conditions, including obesity, MASLD and type 2 diabetes, the circulating levels of hepatokines are increased. It could be speculated that the body increases hepatokine levels as a feedback mechanism to combat dysregulated metabolism. However, the underlying mechanisms driving the elevated levels in metabolic disease are currently unknown. The secretion of follistatin, FGF21 and GDF15 from the liver has been suggested to be stimulated by glucagon and amino acids. In dysregulated metabolic diseases, circulating levels of glucagon and amino acids are often increased and are highly dependent on hepatic steatosis. Increased levels of hepatokines observed in dysregulated metabolic individuals could therefore be attributed to an increase in circulating glucagon, amino acids, or a combination of both.
The study aims to explore the direct and indirect effect of amino acids on the regulation of hepatokines in individuals with and without MASLD. The study evaluates the acute effect of an amino acid infusion with and without a concomitant infusion of the somatostatin analogue octreotide to eliminate endogenous production of glucagon, thus isolating the direct effect of amino acids. ,
The investigators hypothesizes that an amino acid infusion will increase the secretion of hepatokines independent of glucagon.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Evaluating the direct and indirect effect of amino acids on the regulation of hepatokines | Experimental | Other: Evaluating the acute effect of an amino acid infusion with and without a concomitant infusion of the somatostatin analogue octreotide to eliminate endogenous production of glucagonParticipants will be subjected to four experimental days |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female between 25-65 years of age at time of screening
- Body mass index of 18.6-25 kg/m2
- Male or female between 25-65 years of age at time of screening
- Body mass index of 25-40 kg/m2
- Hepatic non-alcoholic steatosis verified by liver biopsy, fibroscan or ultrasound
Key exclusion criteria (25 listed)
- Contraindications for MRI-scan
- Severe liver disease (estimated by FIB4 score > 3.25)
- Type 2 diabetes according to ADA criteria
- Significant history of alcoholism or drug/chemical abuse as per investigators judgement
- Amino acid related diseases
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 |
|---|---|---|
| Evaluating the acute effect of an amino acid infusion with and without a concomitant infusion of the somatostatin analogue octreotide to eliminate endogenous production of glucagonThe experimental days consist of four study days: 1. Assessment of liver fat and visceral fat by magnetic resonance imaging (MRI; 6-point Dixon) (study day A) 2. Somatostatin infusion (4 hours) plus amino acid infusion (45 minutes) (study day B) 3. Saline infusion (4 hours) plus amino acid infusion (45 minutes) (study day C) 4. Somatostatin infusion (4 hours) plus saline infusion (45 minutes) (study day D) The subjects will participate in the experimental days (study day B to D) in randomized order on three different days. For study day B to D, at timepoint t = -75, subjects will receive either; a 240-minute intravenous infusion of a somatostatin analogue (at 200 ng/kg/min (infusion rate will not exceed 1000 µg/hour) or saline. After 75 minutes (timepoint t = 0), the subjects will receive a 45-minute intravenous infusion of amino acids or saline at 3.885 ml/kg/hour. In total, blood will be sampled 11 times over a period of 6 hours and 15 minutes. | Other | Evaluating the direct and indirect effect of amino acids on the regulation of hepatokines |
Primary outcome
The direct (amino acid + somatostatin) versus the indirect (amino acid + placebo) effect of amino acids on circulating levels of follistatin.
Time frame: From blood sample at minute 0 until blood sample at minute 300.
Defined as the difference in incremental AUC0-300 min (iAUC) of follistatin between study day B and study day C in healthy individuals.
6 secondary outcomes
The direct (amino acid + somatostatin) versus the indirect (amino acid + placebo) effect of amino acids on circulating levels of FGF21 and GDF15
Time frame: From blood sample at minute 0 until blood sample at minute 300.
The direct versus the indirect effect of amino acids on circulating levels of hepatokines (follistatin, FGF21 and GDF15).
Time frame: From blood sample at minute 0 until blood sample at minute 300
Differences between healthy and MASLD in the increase in hepatokines during study day B (direct effect of amino acids)
Time frame: From blood sample at minute 0 until blood sample at minute 300
Differences between healthy and MASLD in the increase in hepatokines during study day C (indirect effect of amino acids).
Time frame: From blood sample at minute 0 until blood sample at minute 300
The inhibitory effect of somatostatin versus the stimulatory effect of amino acids on glucagon, insulin and C-peptide levels during study day B in healthy and MASLD.
Time frame: From blood sample at minute -75 until blood sample at minute 45
Differences in glucagon, insulin and C-peptide concentrations between study day B and C in healthy and MASLD
Time frame: From blood sample at minute 0 until blood sample at minute 300
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2026.
- Individual participant dataSharing planned: No. We have not decided to share IPD as this also would require approval from the ethical and data approval committee.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Evaluating the acute effect of an amino acid infusion with and without a concomitant infusion of the somatostatin analogue octreotide to eliminate endogenous production of glucagon in people with Non-Alcoholic Fatty Liver Disease and Obesity, run by University of Copenhagen at 1 site in Denmark.
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 5 inclusion and 25 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: under way, not looking for participants, as of the sponsor's last update on 7 May 2026. 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 Denmark. 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?
This study is still under way. Results are not available in the source record yet.
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?
The direct (amino acid + somatostatin) versus the indirect (amino acid + placebo) effect of amino acids on circulating levels of follistatin. (time frame: From blood sample at minute 0 until blood sample at minute 300.). 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 7 May 2026.