None listed
Conditions
Brief summary
In this study we propose to identify a cohort of 200 men who have a higher than normal PiB in the brain, who are experiencing Subjective Memory Complaints but are not symptomatic for Alzheimer's disease. These men will be treated with testosterone (intramuscular injection), with and without DHA (oral administration) over 56 weeks. The study will evaluate the ability of testosterone & DHA to reduce the levels of LH, beta amyloid levels and subsequent impact on amyloid PIB load in the brain. This study will look at the effects of study treatment on brain images (MRI, PET scans), participants’ scores on psychometric tasks, neuropsychological questionnaires (measurement of memory loss and thinking ability) tests and the effect of treatment on different blood biomarkers.
Interventions
testosterone undecanoate 1000mg/ 4ml (intramuscular injection) every 8 weeks, for 56 weeks
Docosahexaenoic acid (DHA) capsules, 4 capsules per day (total daily dose of 1720mg of DHA) for 56 weeks
There are 3 treatment arms:
Arm 1: Testosterone 1000mg/4 ml plus 1720 mg of DHA
Arm 2: Testosterone 1000mg/4 ml plus placebo-DHA
Arm 3: placebo-testosterone plus placebo-DHA
Sponsors
Lawley Pharmaceuticals
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
Male
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men aged 60 years or over 2. Able to personally read and understand the Participant Information and Consent Form and provide written, signed and dated informed consent to participate in study 3. Able and willing to meet all protocol-required procedures and visits 4. Must have an available informant who is knowledgeable about the participant, who has a minimum of 5 hours contact per week and can provide a reliable way to determine cognitive status of the participant 5. Participants must be PiB-PET positive based on cut-off level of greater than 1.5 SUVR and PET scan done within 6 months at time of commencement of treatment if deemed eligible to participate 6. Mini Mental State Examination (MMSE) greater than 24 as stratified by age and education (i.e. cognitively normal), with inclusion at the discretion of the investigator team (after taking into consideration, age, education, medical, neurological and psychiatric condition) 7. A score of greater than 25 on Memory Complaints Questionnaire (MACQ) to ensure the participants are SMCs 8. Mini- International Neuropsychiatric Interview (depression and anxiety specific) (MINI), Consistent with the absence of major depression at the screening visit according to DSM-IV TR
Exclusion criteria
1. Pathological androgen deficiency (< 8 nmol/L) 2. Baseline serum testosterone measurement >18 nmol/L within 6 months of study screening visit 3. Use of any medication known to: affect testosterone or Sex Hormone Binding Globulin (SHBG) within the previous 1 month or with an underlying condition where there is any possibility that these may be required within the next 12 months 4. Known to have hypothalamo-pituitary or testis pathology (excl. cryptorchidism) 5. Screening ECG that shows evidence of a serious and/or unstable clinical significant condition as determined by the Investigator 6. Laboratory or clinical signs of untreated, clinically significant abnormal thyroid function as deemed by the Investigator 7. Clinically significant folic acid or vitamin B12 deficiency detected within 1 year prior to study consent 8. Diagnosed with severe untreated Obstructive Sleep Apnoea or commenced Continuous positive airway pressure (CPAP) within the previous 6 months 9. Type 1 diabetes mellitus 10. Current clinically significant infection requiring systemic antibiotics 11. Known to be human immunodeficiency virus (HIV) positive 12. Participants should not be included in the study if they are taking chronic narcotic analgesic treatment (including codeine) anti-psychotics, tricyclic antidepressants, dopamine agonists, benzodiazepines, lithium, oral corticosteroids, other anti-cholinergics, cholinesterase inhibitors, paroxetine [an SSRI that is anticholinergic] 13. Clinically significant non-malignant disease that is likely to lead to serious illness or death within 2 years, or in the opinion of the Clinical Investigator, requires other intervention 14. Ongoing episode of major depression or other significant psychiatric or neurological disorders that may have an impact on cognitive performance such as schizophrenia, epilepsy, Parkinson’s disease or clinical episode of stroke. 15. Breast, liver cancer or other malignancy within the last 5 years. Non-melanoma skin cancer (s) treated with curative intent are eligible if disease-free for at least 2 years 16. Prior history of prostate cancer, above Upper Limit of Normal (ULN) for age-adjusted Prostate Specific Antigen (PSA) values or abnormal prostate on digital rectal examination (DRE) 17. Personal or family history of thrombophilia, or taking anticoagulants, other than low dose Aspirin (100mg) for cardiovascular prophylaxis 18. > 1.5 X Upper Limit of Normal coagulation profile 19. Major cardiovascular event within the previous 6 months, or active cardiac disease 20. Elevated blood pressure (above 160/100mmHg) at screening 21. Haematocrit > 52% and Haemoglobin > 18.5 g/dL, or platelet counts <100,000 cells/uL 22. ALT, GGT, Bilirubin or ALP > 3 times upper limit of normal (ULN) 23. Known chronic viral hepatitis 24. eGFR < 50 mL/minute 25. Treatment with investigational medication within 2 months prior to informed consent 26. Known history of drug or alcohol abuse within 6 months prior to the time of screening 27. BMI > 35 28. Lumbar spinal surgery within the last 6 months prior to screening, or any lumbar spinal surgery that interferes with anatomy of the inter-vertebral spaces 29. History of chronic or repeat cerebrospinal fluid leakage following previous lumbar puncture 30. Unable to have an MRI
Outcome results
None listed