Prometeo-Hg

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Consorcio Centro De Investigacion Biomedica En Red

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

19 Dec 2024 → ongoing

Decision date (initial)

2024-12-19

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516561-37-01

EudraCT number

2021-000152-19

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Diagnosis, Efficacy, Safety, Dose response, Pharmacogenomic

To determine which of the three models of therapeutic intervention induces a greater sustained regression of fatty liver associated with long-term metabolic disease (18 months) measured by non-invasive techniques (MRI) in patients with Metabolic Associated Fatty Liver Disease and prediabetes.

Secondary objectives 4

1. Investigate whether the variations of the genes involved consistently determine and / or condition the degree of response to dietary treatment with a hypocaloric Mediterranean diet and to drug treatment with metformin and pioglitazone.
2. Explore the changes induced by diet and each pharmacological treatment in the concentration of metabolites derived from mitochondrial function, intestinal microbiota.
3. To determine whether the changes in the concentration of alpha-ketoglutarate and other metabolites derived from the mitochondria induced by the therapeutic intervention models are associated with the progression or regression of fatty liver.
4. Establish which of the three models of therapeutic intervention induces an improvement in the pathogenic factors associated with the development of non-alcoholic fatty liver: peripheral insulin resistance, hepatic insulin resistance, adipose tissue dysfunction, intestinal microbiota.

Conditions and MedDRA coding

Metabolic Associated Fatty Liver Disease with prediabetes.

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients with HGADM according to the clinical criteria of the International Expert Consensus Statement.
2. Age from 18 to 75 years.
3. Men and postmenopausal women.
4. Evidence of significant nonalcoholic fatty liver disease, defined by a proportional attenuation of the intrahepatic signal> 10% observed by magnetic resonance imaging.
5. Overweight or obese with BMI 25-40 kg / m2
6. Presence of Prediabetes according to the ADA criteria (fasting blood glucose 100-125 mg / dl or HbA1c 5.7% -6.4% or blood glucose 140-199 mg / dl at 2 hours after SOG).

Exclusion criteria 17

1. Patients with a life expectancy that is less than 5 years.
2. History of alcohol consumption> 30 g / day in men or> 20 g / day in women for 3 consecutive months in the last year.
3. Inability to maintain complete alcohol withdrawal during the study period.
4. Patients with decompensated liver cirrhosis or altered liver function (BiT> 2mg / dL, INR> 1.3).
5. Treatment with drugs potentially associated with fatty liver disease in the previous 3 months (amiodarone, corticosteroids, methotrexate, tetracyclines, tamoxifen, oral contraceptives).
6. History of hepatocarcinoma or malignancy in the 5 years prior to inclusion in the study, except cervical carcinoma in situ and basal cell carcinoma or cutaneous basal cell carcinoma.
7. Being undergoing chemotherapy or radiotherapy treatment.
8. Other causes of fatty liver: fasting, hemochromatosis, Wilson's disease, or autoimmune hepatitis.
9. Active evidence of HBV or HCV infection
10. Severe heart failure; NYHA functional class III or IV.
11. Type 1 and 2 diabetes.
12. Taking other antidiabetic drugs.
13. Chronic diseases not related to metabolic disease: severe psychiatric, chronic kidney failure (GFR <45 ml / min), chronic respiratory failure, chronic processes necessary for treatment that can modify glucose metabolism.
14. Severe cardiovascular, renal, endocrine, gastrointestinal, or psychiatric comorbidity that, in the opinion of the investigator, may make adherence to treatment or interpretation of results difficult.
15. Participants in other clinical trials in the 30 days prior to the start of the study.
16. Sexually active men with a woman of childbearing age who plans to become pregnant.
17. Patients with limitation to follow the protocol for any reason.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Significant decrease in the amount of intrahepatic fat (> 20%) in the absence of liver fibrosis progression.

Secondary endpoints 6

1. Study of insulin resistance and adipose tissue dysfunction
2. Search for non-invasive markers of efficacy of the proposed treatments among circulating metabolites (metabolomic and lipidomic methods).
3. Study of the intestinal microbiota.
4. Pharmacogenetic study: influence of genetic variations on the degree of therapeutic response to drugs.
5. Study of bioimpedanciometry.
6. Collection of adverse events potentially related to the medication and its administration.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Consorcio Centro De Investigacion Biomedica En Red

Sponsor organisation

Consorcio Centro De Investigacion Biomedica En Red

Address

Pab 11, Avenida De Monforte De Lemos 3-5 Avenida De Monforte De Lemos 3-5

City

Madrid

Postcode

28029

Country

Spain

Scientific contact point

Organisation

Consorcio Centro De Investigacion Biomedica En Red

Contact name

Projects Department

Public contact point

Organisation

Consorcio Centro De Investigacion Biomedica En Red

Contact name

Projects Department

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications