Testosterone Replacement in Non-alcoholic Steatohepatitis (TEREPINS)

NCT01919294 | Completed Phase 2 DMC

• 2 other identifiers: STH160372012-002564-27
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The main research questions are: In hypogonadal men with non-alcoholic steatohepatitis (NASH), does Testosterone Replacement Therapy (TRT), given for 12 months

1. 1.improve severity of steatosis on liver biopsy (Primary Question)?
2. 2.improve severity of associated steatohepatitis on liver biopsy?
3. 3.reduce liver fat content as assessed by proton Magnetic Resonance Spectroscopy (1H-MRS)?

Conditions

Nonalcoholic Steatohepatitis; Hypogonadism

Keywords

nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; hypogonadism; testosterone replacement therapy

Outcome Measures

Primary Outcomes (1)

• steatosis histology

  Proportion of patients in whom severity of steatohepatitis improves with testosterone replacement therapy, assessed by liver biopsy

  baseline and 12 months

Secondary Outcomes (7)

• Proportion of patients in whom liver inflammation improves

  baseline and 12 months

• Proportion of patients in whom liver ballooning improves

  baseline and 12 months

• Proportion of patients in whom liver fibrosis improves

  baseline and 12 months

• Change in fat content of liver

  baseline and 12 months

• Change in HOMA index

  baseline and 12 months

Other Outcomes (1)

• Study recruitment rate

  24 months

Study Arms (1)

testosterone undecanoate

EXPERIMENTAL

Open label testosterone injection. Testosterone Undecanoate (1 g in 4 ml oily base) will be given as slow (2 minute) intramuscular injections (Nebido, manufactured by Bayer-Schering). These will be administered by the study investigator or designated research nurse at time zero (baseline visit 2) and after 6, 18, 30 and 42 weeks.

Drug: testosterone undecanoate

Interventions

testosterone undecanoate DRUG

Preparation: 1 gram in 4 ml of oily base. Requires no special storage conditions. Proposed regime: 1 mg as a single intramuscular injection at 0, 6, 18, 30 and 42 weeks

Also known as: Nebido

testosterone undecanoate

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Negative serological tests for hepatitis Bs ag and C antibody.
• 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.
• Liver biopsy, performed as part of clinical management within 6 months of recruitment, which shows all of: (a) steatosis (Kleiner grade 2 or 3); (b) NASH (combined intralobular inflammation and hepatocyte ballooning score of \>1); (c) fibrosis Ishak stage \<4; and (d) no evidence to suggest another major liver disease.
• Hypotestosteronaemia, defined by total serum testosterone \<11 nmol/L . Investigators predict that this will include about 25% of men with NAFLD as defined above.

You may not qualify if:

• Inability to give informed consent.
• Age \<18 or \>75 years.
• Symptomatic sexual dysfunction.
• 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).
• Space occupying lesion on ultrasound with any suspicion of malignancy.
• Evidence of other chronic liver diseases pace occupying lesion on ultrasound with any suspicion of malignancy.
• Prostatic nodule or mass on PR examination unless full urological examination rules our prostate cancer
• Serum PSA or alpha feta protein above the age-specific normal range
• Carcinoma of male breast
• Taking medications (amiodarone, anti-retrovirals, sodium alproate, corticosteroids, tamoxifen) the previous 3 months (known to improve steatosis).
• 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.
• Severe or complicated obesity, likely requiring bariatric surgery in next 2 years.
• LH/FSH levels, raising the possibility of primary pituitary disease.
• Subject trying to or hoping to conceive within next 18 months.
• Haematocrit of \>0.54

Sponsors & Collaborators

• Sheffield Teaching Hospitals NHS Foundation Trust: lead
• Bayer: collaborator

Study Sites (1)

Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, South Yorkshire, S10 2JF, United Kingdom

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Hypogonadism

Interventions

testosterone undecanoate

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Gonadal Disorders; Endocrine System Diseases

Study Officials

• Dermot Gleeson, MD

  Sheffield Teaching Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2013
• First Posted: August 9, 2013
• Study Start: July 1, 2013
• Primary Completion: January 30, 2017
• Study Completion: January 30, 2017
• Last Updated: April 26, 2017

Record last verified: 2017-04

Locations

GB (1)