Testosterone Replacement in men with liver disease

Phase 1

• Conditions: on alcoholic fatty liver disease (NAFLD) in men with low serum testosterone levels; Therapeutic area: Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]

• Registration Number: EUCTR2012-002564-27-GB
• Lead Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-01-04
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 10

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 <446; and (d) no evidence to suggest another major liver disease.
5.Hypotestosteronaemia, defined by total serum testosterone <11 ng/L40 . We predict that this will include about 25% of men with NAFLD as defined above.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion Criteria

1.Inability to give informed consent.
2.Age <18 or >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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified