NAFLD Among Patients With Chronic Kidney Disease and the Effect of Kidney Transplantation

NCT03866421 | Terminated DMC FDA Device

• 1 other identifier: NAFLD and CKD - Study 2
• Study Type: observational
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries affecting approximately 30 % of the general adult population. It represents an important pathogenic factor in the development of type 2-diabetes and is associated with a high risk of cardiovascular disease. Previous studies of patients with chronic kidney disease (CKD) have demonstrated an increased risk for NAFLD and the presence of both CKD and NAFLD is likely to increase the risk for cardiovascular disease. The present protocol describes a study of the prevalence and etiology of NAFLD among patients scheduled for kidney transplantation and the possible effect of kidney transplantation on NAFLD. The project is a prospective cohort study. The effect of kidney transplantation in patients with prediabetes or normal glucose tolerance compared to healthy controls will be examined regarding development and progression of fat accumulation in the liver. Fat accumulation in the liver will be determined by magnetic resonance (MR) spectroscopy and the prevalence of NAFLD in the two groups will be investigated. A continuous glucose monitoring (CGM) for four days, Dual Energy X-ray Absorptiometry (DEXA) scanning, fibro scanning of the liver, bile acid analysis, metabolomic and lipidomic analysis will also be performed. An oral glucose tolerance test (OGTT) and an intra venous glucose infusion (IIGI) will be performed.

Conditions

Non-Alcoholic Fatty Liver Disease; Chronic Kidney Diseases; PreDiabetes; Kidney Transplant

Outcome Measures

Primary Outcomes (1)

• Changes in relative lipid signal measured by MR spectroscopy in the liver before kidney transplantation compared with three and twelve months after kidney transplantation

  Liver signal is measured by MR spectroscopy (the non-invasive method for determination of NAFLD)

  Kidney transplanted patients: 3 visits á 1 hour (baseline (before transplantation), three months and twelve months after transplantation), Control group: One hour

Secondary Outcomes (14)

• Prevalence of fibrosis in the liver before and after kidney transplantation measured by fibroscan.

  Kidney transplanted patients: 3 visits x 15 minutes (baseline (before transplantation), three months and twelve months after transplantation), Control group: 15 minutes

• Prevalence of fibrosis in the liver before and after kidney transplantation measured in clinical index (NAFLD fibrosis score).

  Kidney transplanted patients: 3 visits á one day (baseline (before transplantation), three months and twelve months after transplantation), Control group: One day

• Prevalence of fibrosis in the liver before and after kidney transplantation measured by clinical index (FIB-4 score).

  Kidney transplanted patients: 3 visits á one day (baseline (before transplantation), three months and twelve months after transplantation), Control group: One day

• Glycemic variability associated with NAFLD, as measured by MR spectroscopy, before and after kidney transplantation

  Kidney transplanted patients: 4 days x3 visits (baseline (before transplantation), three months and twelve months after transplantation), Control group: 4 days

• Mean glucose associated with NAFLD, as measured by MR spectroscopy, before and after kidney transplantation

  Kidney transplanted patients: 4 days x3 visits (baseline (before transplantation), three months and twelve months after transplantation), Control group: 4 days

Study Arms (2)

Kidney transplanted patients

Number of patients: 16 Patients on the waiting list for kidney transplantation with a living donor. The patients are screened with an OGTT before participation in the study, thereby excluding patients with diabetes mellitus. Patients in this group are examined three times (baseline (before transplantation) and after three and twelve months after transplantation). Same interventions as in the control Group. Including/ Exclusion criteria are listed under the section "Eligibility"

Diagnostic Test: MR spectroscopy of the liver; Diagnostic Test: Fibroscan of the liver; Device: Continuous glucose monitoring (CGM) for four days.; Diagnostic Test: Oral glucose tolerance test (OGTT); Diagnostic Test: Intra venous glucose infusion (IIGI); Radiation: Dual Energy X-ray Absorptiometry (DEXA) scan; Biological: Blood samples; Other: Clinical and demographic data

Control group

Number of patients: 16 Participants in this group are matched on age and BMI according to the kidney transplanted patients. Participants are screened with an OGTT before participation since only persons with normal glucose tolerance may be included in the study. Furthermore, participants have to have normal kidney function. Participants in this group are only examined once. Same interventions as in the kidney transplanted patient group

Diagnostic Test: MR spectroscopy of the liver; Diagnostic Test: Fibroscan of the liver; Device: Continuous glucose monitoring (CGM) for four days.; Diagnostic Test: Oral glucose tolerance test (OGTT); Diagnostic Test: Intra venous glucose infusion (IIGI); Radiation: Dual Energy X-ray Absorptiometry (DEXA) scan; Biological: Blood samples; Other: Clinical and demographic data

Interventions

MR spectroscopy of the liver DIAGNOSTIC_TEST

Magnetic resonance spectroscopy of the liver. Golden standard for non-invasive determination of NAFLD

Control group; Kidney transplanted patients

Fibroscan of the liver DIAGNOSTIC_TEST

Transient Elastography for Measurement of liver fibrosis.

Control group; Kidney transplanted patients

Continuous glucose monitoring (CGM) for four days. DEVICE

CGM is attached to the abdominal skin for four days. Afterwards data is converted and analysed in a computer program.

Control group; Kidney transplanted patients

Oral glucose tolerance test (OGTT) DIAGNOSTIC_TEST

OGTT with incretin hormones. Measured for three hours.

Control group; Kidney transplanted patients

Intra venous glucose infusion (IIGI) DIAGNOSTIC_TEST

This test is combined with the OGTT to compare responses of parenteral vs enteral stimulation. The test is followed by a bolus of 5 g of L-arginin.

Control group; Kidney transplanted patients

Dual Energy X-ray Absorptiometry (DEXA) scan RADIATION

DEXA-scan of the body composition.

Control group; Kidney transplanted patients

Blood samples BIOLOGICAL

Immediately analyse of basic lab data. Later analyses for glucagon, amino acids, bile acids, lipidomics and metabolomics.

Control group; Kidney transplanted patients

Clinical and demographic data OTHER

Measurements of blood pressure, pulse, height, weight.

Control group; Kidney transplanted patients

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Total number of participants: 32 divided in two Groups: * 16 kidney transplanted patients * 16 healthy control persons The 16 kidney transplanted patients are scheduled for kidney transplantation with a living donor at Rigshospitalet. They will be recruited from the donor- and recipient register for kidney transplantation at Rigshospitalet and Herlev Hospital. The 16 healthy persons in the control group will be recruited through advertisement. All participants are screened by an OGTT before inclusion in the study.

You may qualify if:

• Outpatient at the department of nephrology at either Rigshospitalet or Herlev Hospital scheduled for a kidney transplantation with a living donor
• Impaired glucose tolerance: fasting glucose concentration \< 7,0 mmol/ l and a 2-hour glucose load ≥ 7,8 mmol/ l and \< 11,1 mmol/ l OR Impaired fasting glycaemia: Fasting blood glucose ≥ 6,1 mmol/ l and \< 7,0 mmol/ l and a 2-hour glucose load \< 7,8 mmol/ l OR Normal glucose tolerance: fasting glucose concentration \< 6,1 mmol/ l and a 2-hour glucose load \< 7,8 mmol/ l.
• Normal kidney function
• Normal glucose tolerance

You may not qualify if:

• End stage liver disease as diagnosed by MELD (model for end stage liver disease) criteria OR
• At the waiting list for liver transplantation OR
• Daily alcohol intake above 20 g and 30 g for women and men respectively OR
• Known hepatitis A, B or C or hepatocellular carcinoma or other known liver disease OR
• Pregnancy OR
• Weight \> 130 kg OR
• Implanted pacemaker

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Steno Diabetes Center Copenhagen: collaborator
• Herlev and Gentofte Hospital: collaborator
• The Novo Nordisk Foundation Center for Basic Metabolic Research: collaborator

Study Sites (1)

Department of Nephrology

Copenhagen, 2100, Denmark

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples will be collected for both immediately analyses (basic lab data) and later analyses (bile acids, glucagon, amino acids, GLP-1, GIP, lipidomics and metabolomics) and stored for 10 years whereafter they will be destroyed.

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Renal Insufficiency, Chronic; Prediabetic State

Interventions

Continuous Glucose Monitoring; Glucose Tolerance Test; Absorptiometry, Photon; Blood Specimen Collection; Demography

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Monitoring, Physiologic; Investigative Techniques; Radiography; Diagnostic Imaging; Densitometry; Photometry; Chemistry Techniques, Analytical; Specimen Handling; Punctures; Surgical Procedures, Operative; Population Characteristics; Epidemiologic Measurements; Public Health; Environment and Public Health

Study Officials

• Bo Feldt-Rasmussen, Professor

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Head of the Department of Nephrology

Study Record Dates

• First Submitted: January 30, 2019
• First Posted: March 7, 2019
• Study Start: May 29, 2019
• Primary Completion: February 25, 2021
• Study Completion: March 31, 2022
• Last Updated: May 2, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)