Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Effect of Curcumin on the Development of Prednisolone-induced Hepatic Insulin Resistance (CURPRED)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04315350
Recruitment Status : Recruiting
First Posted : March 19, 2020
Last Update Posted : March 19, 2020
Sponsor:
Information provided by (Responsible Party):
Pernille Høgh Hellmann, University Hospital, Gentofte, Copenhagen

Brief Summary:
The aim of this study is to investigate whether ingestion of curcumin will prevent hepatic insulin resistance (assessed by homeostatic model assessment of insulin resistance (HOMA-IR)) induced by short-term oral glucocorticoid (prednisolone) administration in overweight and obese participants. As a secondary endpoint it will be investigated if prednisolone administration induce or worsen the degree of NAFLD in overweight or obese participants using magnetic resonance (MR) spectroscopy (MRS), and if curcumin can ameliorate this effect. Also, the possible anti-inflammatory effect of curcumin will be elucidated as a range of inflammatory markers before and after intervention will be measured. Thus, prednisolone treatment is used as a model of development of pre-diabetes.

Condition or disease Intervention/treatment Phase
Insulin Resistance Non-Alcoholic Fatty Liver Disease Drug: Curcumin Liposome Drug: Prednisolone Drug: Placebos Not Applicable

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: After study day 1, participants are randomized (1:1:1) to one of three treatments: 1) Prednisolon and Curcumin, 2) Prednisolon and placebo or 3) Placebo and placebo.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The Effect of Curcumin on the Development of Prednisolone-induced Hepatic Insulin Resistance in Overweight and Obese Participants
Actual Study Start Date : December 1, 2019
Estimated Primary Completion Date : December 1, 2020
Estimated Study Completion Date : December 1, 2021


Arm Intervention/treatment
Experimental: Curcumin
Participant receives both curcumin and prednisolone. Curcumin for 11 days, prednisolone for 10 days. Curcumin: 2 tablets (each contains 100 mg curcumin) twice daily. Prednisolon: 50 mg (capsule) every morning
Drug: Curcumin Liposome
Curcumin is given together with prednisolone

Prednisolon
Participant receives prednisolone and curcumin-placebo. Curcumin-placebo for 11 days, prednisolone for 10 days. Curcumin-placebo: 2 tablets twice daily. Prednisolon: 50 mg (capsule) every morning
Drug: Prednisolone
Prednisolone is given together with curcumin-placebo

Placebo Comparator: Placebo
Participant receives prednisolone.placebo and curcumin-placebo. Curcumin-placebo for 11 days, prednisolone-placebo for 10 days. Curcumin-placebo: 2 tablets twice daily. Prednisolon-placebo: One capsule every morning.
Drug: Placebos
Prednisolone-placebo is given together with curcumin-placebo




Primary Outcome Measures :
  1. HOMA-IR [ Time Frame: 12-14 days ]
    homeostatic model assessment of insulin resistance is calculated before and after intervention


Secondary Outcome Measures :
  1. steatosis [ Time Frame: 12-20 days ]
    Measured by MR spectroscopy of the liver (unit: %)

  2. liver stiffness [ Time Frame: 12-14 days ]
    Measured by FibroScan (unit: kPa)

  3. concentration of alanine transaminase [ Time Frame: 12-14 days ]
    Blood sample

  4. concentration of aspartate transaminase [ Time Frame: 12-14 days ]
    Blood sample

  5. concentration of creatine kinase [ Time Frame: 12-14 days ]
    Blood sample

  6. glucagon levels under oral glucose tolerance test [ Time Frame: 12-14 days ]
    Blood sample

  7. concentration of amino acids under oral glucose tolerance test [ Time Frame: 12-14 days ]
    Blood sample

  8. urea concentration in plasma [ Time Frame: 12-14 days ]
    Blood sample

  9. urea concentration in urin [ Time Frame: 12-14 days ]
    Urin sample

  10. urea production [ Time Frame: 12-14 days ]
    Estimated by collecting urin for 4-5 hours, measuring volume of urine and urea concentration

  11. concentration of gamma glutamyl transferase [ Time Frame: 12-14 days ]
    Blood sample

  12. concentration of blood lipids [ Time Frame: 12-14 days ]
    Blood sample

  13. gut hormone concentration during oral glucose tolerance test [ Time Frame: 12-14 days ]
    blood sample

  14. concentration of inflammation markers (interleukines and high sensitivity CRP and TNF alpha) [ Time Frame: 12-14 days ]
    blood sample

  15. concentration of serum biomarkers of non-alcoholic steatohepatitis [ Time Frame: 12-14 days ]
    blood sample

  16. concentration of serum biomarkers of fibrosis in the liver [ Time Frame: 12-14 days ]
    blood sample

  17. concentration of fasting glucose [ Time Frame: 12-14 days ]
    blood sample

  18. concentration of glucose levels during oral glucose tolerance test [ Time Frame: 12-14 days ]
    blood sample

  19. concentration of serum bone markers [ Time Frame: 12-14 days ]
    blood sample

  20. concentration of fibroblast growth factors [ Time Frame: 12-14 days ]
    blood sample

  21. Gut microbiota analysis (abundance) [ Time Frame: 12-20 days ]
    Feces sample before and after intervention

  22. Gut microbiota analysis (alpha and beta diversity) [ Time Frame: 12-20 days ]
    Feces sample before and after intervention

  23. Gut microbiota analysis (link to phenotype of interest) [ Time Frame: 12-20 days ]
    Feces sample before and after intervention

  24. Glucose measurement by continuous monitor [ Time Frame: 11-14 days ]
    subcutaneously, interstitial measurement (concentration of glucose) every 15 minutes in the intervention period

  25. intra ocular eye pressure in both eyes [ Time Frame: 12-14 days ]
    icare 100 tonometer measurement (unit: mmHg)

  26. BOdy composition (fat, water, skeletal muscle mass, fat-free mass) [ Time Frame: 12-14 days ]
    measured by bioimpedance (units: kg and %)

  27. visceral fat tissue amount [ Time Frame: 12-20 days ]
    MR-spectroscopy measurement (unit: cm3 at L3-level, 1 cm thick slice)

  28. subcutaneous fat tissue amount [ Time Frame: 12-20 days ]
    MR-spectroscopy measurement (unit: cm3 at L3-level, 1 cm thick slice)

  29. Body weight [ Time Frame: 12-14 days ]
    Body weight (unit: kg)

  30. Body mass index [ Time Frame: 12-14 days ]
    (kg/m2)

  31. waist circumference [ Time Frame: 12-14 days ]
    (unit: cm)

  32. hip circumference [ Time Frame: 12-14 days ]
    (unit: cm)

  33. Questionnaire during oral glucose tolerance test every 30 minutes and ten minutes after ad libitum meal: How hungry do you feel? Range: I'm not hungry at all - I've never been more hungry [ Time Frame: 12-14 days ]
    visual analogue scale evaluation (no visible numbers/points, just a clear line)

  34. Questionnaire during oral glucose tolerance test every 30 minutes and ten minutes after ad libitum meal: How full do you feel? Range: I have a big hole in my stomach - I can not eat one single bite more [ Time Frame: 12-14 days ]
    visual analogue scale evaluation (no visible numbers/points, just a clear line)

  35. Questionnaire during oral glucose tolerance test every 30 minutes and ten minutes after ad libitum meal: How filled up do you feel? Range: Not filled up at all - totally filled up [ Time Frame: 12-14 days ]
    visual analogue scale evaluation (no visible numbers/points, just a clear line)

  36. Questionnaire during oral glucose tolerance test every 30 minutes and ten minutes after ad libitum meal: How much do you think you can eat? Range: nothing at all - really much [ Time Frame: 12-14 days ]
    visual analogue scale evaluation (no visible numbers/points, just a clear line)

  37. Questionnaire during oral glucose tolerance test every 30 minutes and ten minutes after ad libitum meal: How do you feel? Range: Really bad - really good [ Time Frame: 12-14 days ]
    visual analogue scale evaluation (no visible numbers/points, just a clear line)

  38. Questionnaire during oral glucose tolerance test every 30 minutes and ten minutes after ad libitum meal: do you feel nausious? Range: yes, very much - no, not at all [ Time Frame: 12-14 days ]
    visual analogue scale evaluation (no visible numbers/points, just a clear line)

  39. Questionnaire during oral glucose tolerance test every 30 minutes and ten minutes after ad libitum meal: How thirsty do you feel? Range: Not thirsty at all - very thirsty [ Time Frame: 12-14 days ]
    visual analogue scale evaluation (no visible numbers/points, just a clear line)

  40. Questionnaire during ad libitum meal: appearance of the meal: Range: Not appetizing - very appetizing [ Time Frame: 12-14 days ]
    visual analogue scale evaluation (no visible numbers/points, just a clear line)

  41. Questionnaire during ad libitum meal: Smell of the meal: Range: Not appetizing - very appetizing [ Time Frame: 12-14 days ]
    visual analogue scale evaluation (no visible numbers/points, just a clear line)

  42. Questionnaire during ad libitum meal: Taste of the meal: Range: Bad - Good [ Time Frame: 12-14 days ]
    visual analogue scale evaluation (no visible numbers/points, just a clear line)

  43. Questionnaire during ad libitum meal: Does the meal have unwanted taste? Range: no, not at all - yes, a lot [ Time Frame: 12-14 days ]
    visual analogue scale evaluation (no visible numbers/points, just a clear line)

  44. Questionnaire during ad libitum meal: How is the overall impression of the meal? Range: not appetizing - Very appetizing [ Time Frame: 12-14 days ]
    visual analogue scale evaluation (no visible numbers/points, just a clear line)

  45. Food consumption [ Time Frame: 12-14 days ]
    Evaluated by calculating ingested meal at ad libitum meal at test days (unit: grams and calories)

  46. systolic blood pressure [ Time Frame: 12-14 days ]
    unit: mmHg

  47. diastolic blood pressure [ Time Frame: 12-14 days ]
    unit: mmHg

  48. heart rate [ Time Frame: 12-14 days ]
    Unit: beats per minute

  49. resting energy expenditure (kcal/day) measured by inderect calorimetry [ Time Frame: 12-14 days ]
    Measured for 15 minutes at test days.

  50. Evaluation of food consumption the day before test day. Participant will fill out diary of all foods and drinks consumed. [ Time Frame: 12-14 days ]
    24 hour recall questionnaire

  51. Questionnaire regarding fullness before bedtime the day before test day: how hungry were you before bed time? Range: Very hungry - not hungry at all [ Time Frame: 12-14 days ]
    Visual analogue scale (no points/number visible, just a clear line)

  52. Evaluation of physical activity the day before test day. Participant will fill out diary of all physical activities including activity intensity. [ Time Frame: 12-14 days ]
    24 hour recall questionnaire

  53. concentration of c-peptide during oral glucose tolerance test [ Time Frame: 12-14 days ]
    blood sample

  54. concentration of lactate dehydrogenase [ Time Frame: 12-14 days ]
    blood sample

  55. concentration of free fatty acids during oral glucose tolerance test [ Time Frame: 12-14 days ]
    blood sample

  56. concentration of alkaline phosphatase [ Time Frame: 12-14 days ]
    blood sample

  57. concentration of albumin [ Time Frame: 12-14 days ]
    blood sample

  58. concentration of insulin fasting [ Time Frame: 12-14 days ]
    blood sample

  59. levels of insulin during oral glucose tolerance test [ Time Frame: 12-14 days ]
    blood sample



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Only males are included
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Body mass index (BMI) >24.9 kg/m2
  • Haemoglobin ≥7.5 mmol/l
  • Written informed consent

Exclusion Criteria:

  • Use of glucose-lowering drugs, lipid-lowering drugs, warfarin, clopidogrel or non-vitamin K anti-coagulants
  • Frequent use of anti-inflammatory drugs the last two months prior to inclusion, judged by the investigator
  • Treatment with drugs with potential steatogenic side-effects within two months prior to inclusion
  • Use of medication known to interact with prednisolone
  • Use of curcumin-containing food supplements or other natural products that could cause confounding as evaluated by investigator
  • Any regular drug treatment that cannot be discontinued for minimum 18 hours
  • Previous diagnosis of T2D
  • Diabetes (HbA1c ≥ 48 mmol/mol) found at screening
  • Known viral, inherited or alcoholic liver disease, or any other condition known to affect liver
  • Intake of more than 21 units of alcohol per week
  • Nephropathy (eGFR < 60 ml/min/1.73 m² and/or urine albumin > 20 mg/l)
  • In a weight management program, or planning to change life style, alcohol habits or eating habits during the course of the study
  • Implanted metal objects contraindicative of MRS Claustrophobia
  • Any condition that the investigator think would interfere with trial participation or with the safety of the participant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04315350


Contacts
Layout table for location contacts
Contact: Pernille H Hellmann, MD +45 20911792 pernille.hoegh.hellmann@regionh.dk
Contact: Filip K Knop, Professor +45 38674266 filip.krag.knop.01@regionh.dk

Locations
Layout table for location information
Denmark
Center for Clinical Metabolic Research Recruiting
Hellerup, Denmark, 2900
Contact: Pernille H Hellmann, MD    +45 20911792    pernille.hoegh.hellmann@regionh.dk   
Contact: Filip K Knop, Professor    +45 38674266    filip.krag.knop.01@regionh.dk   
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
Investigators
Layout table for investigator information
Principal Investigator: Filip K Knop, Professor Gentofte university hospital, Hellerup, Denmark

Layout table for additonal information
Responsible Party: Pernille Høgh Hellmann, Medical Doctor, primary investigator, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT04315350    
Other Study ID Numbers: H-19017550
First Posted: March 19, 2020    Key Record Dates
Last Update Posted: March 19, 2020
Last Verified: March 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Insulin Resistance
Digestive System Diseases
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Prednisolone
Methylprednisolone Acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Curcumin
Prednisolone hemisuccinate
Prednisolone phosphate
Physiological Effects of Drugs
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Anti-Inflammatory Agents, Non-Steroidal