Non alcoholic fatty liver disease (NAFLD) in men with low serum testosterone levels
Conditions
Interventions
Trade Name: Nebido
Product Name: Testosterone Undecanoate (Nebido)
Product Code: not applicable
Pharmaceutical Form: Injection
INN or Pr
Sponsors
Sheffield Teaching Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Men will be recruited with hypogonadism and NAFLD based on all of: 1. Abnormal serum ALT on >2 occasions over at least 3 months, despite standard lifestyle advice when appropriate, in regard to moderation of alcohol intake, weight reduction and exercise. 2. Negative serological tests for hepatitis Bs ag and C antibody. 3. Alcohol consumption >21 units per week for no more than 2 week in the last year and for no more than 3 months of the past 5 years, assessed using a lifetime alcohol consumption questionnaire 44. 4. Liver biopsy, performed as part of clinical management within 6 months of recruitment, which shows all of: (a) steatosis (Kleiner grade 2 or 3)45; (b) NASH (combined intralobular inflammation and hepatocyte ballooning score of >1)45; (c) fibrosis Ishak stage =65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: 1. Inability to give informed consent. 2. Age 75 years. 3. Symptomatic sexual dysfunction. 4. Cirrhosis either on baseline liver biopsy (Ishak score 5-6) or suggested by presence of varices, by ultrasound (small shrunken liver, ascites, splenomegaly) or by liver decompensation (encephalopathy, abnormal serum direct bilirubin, albumin or prothrombin time). 5. Space occupying lesion on ultrasound with any suspicion of malignancy. 6. Evidence of other chronic liver diseases pace occupying lesion on ultrasound with any suspicion of malignancy. 7. Prostatic nodule or mass on PR examination unless full urological examination rules our prostate cancer 8. Serum PSA or alpha feta protein above the age-specific normal range 9. Carcinoma of male breast 10. Taking medications (amiodarone, anti-retrovirals, sodium alproate, corticosteroids, tamoxifen) the previous 3 months (known to improve steatosis). 11. Diabetes or hyperlipidaemia, where therapy has been changed within the last 12 months or with suboptimal control anticipating the need for change in therapy during the study. 12. Severe or complicated obesity, likely requiring bariatric surgery in next 2 years. 13. LH/FSH levels, raising the possibility of primary pituitary disease. 14. Subject trying to or hoping to conceive within next 18 months. 15. Haematocrit of >0.54 16. History of any of the following: Sleep apnoea, breast or prostate or liver cancer, congestive heart failure, chronic renal failure (serum creatinine >150), severe chronic obstructive airways disease, uncontrolled hypertension epilepsy depression or migraine. 17. Severe co morbidity likely in the opinion of the investigators to reduce life expectancy to <10 years. 18. Hypersensitivity to active agent or to any of the excipients. Patients in whom H-MRS is contraindicated (e.g. due to a pacemaker) will be eligible for the trial but H-MRS will not be performed with those participants.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In hypogonadal men with non-alcoholic steatohepatitis (NASH), does Testosterone Replacement Therapy (TRT), given for 12 months, improve severity of steatosis assessed by liver biopsy?; Secondary Objective: In hypogonadal men with non-alcoholic steatohepatitis (NASH), does Testosterone Replacement Therapy (TRT), given for 12 months, - improve severity of associated steatohepatitis on liver biopsy? - reduce liver fat content as assessed by proton Magnetic Resonance Spectroscopy (1H-MRS)? The work proposed here is an open pilot study of 10 patients, the main aim of which is to assess the effect size of TRT in regard to these end points (regarding which there are no published data), thereby allowing power calculations for a more definitive phase II trial. Other aims would be assessing recruitment and consent rates, which would also inform the design of the larger study. ; Primary end point(s): Improvement in severity of steatosis on repeat liver biopsy after 52 weeks. ;Timepoint(s) of evaluation of this end point: This will he assessed by grading fat infiltration on repeat liver biopsy after 52 weeks of treatment with testosterone replacement therapy, which will be compared to baseline liver biopsy (performed for clinical diagnosis). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Proportion of patients in whom liver inflammation, ballooning and fibrosis respectively improve 2. Change in fat content of liver by MR spectroscopy and its correlation with steatosis on liver biopsy 3. Change in HOMA index 4. Change in serum liver enzymes 5. Adverse events (B) Eligibility, recruitment and data completeness rates ;Timepoint(s) of evaluation of this end point: 12 months as per primary endpoint described above. | — |
Countries
United Kingdom
Contacts
Public ContactJim Lithgow
Sheffield Teaching Hospitals NHS Foundation Trust
Outcome results
None listed