None listed
Conditions
Brief summary
Major Depressive Disorder is a leading cause of death and disability worldwide. Although the uptake of treatment varies between nations and amongst socio-demographic groups, overall there is a considerable unmet need for treatment. Many reasons exist for this, including lack of education, social stigma, limited treatment options and unaffordability. There is increasing interest in repurposing and repositioning of extant compounds in the management of mental illnesses, partly due to the retreat of pharmaceutical companies in neurosciences potentially as a result of lengthy approval processes for new discoveries, poor or delayed returns on investment relative to the investment risks, and logistical barriers. The investigational agents, Naltrexone and Flumazenil, both have existing uses in medicine and psychiatry around the world, but both may offer unique mechanisms of action in the treatment of depression contingent upon the doses utilised. Both have short elimination half-lives in the human body and have either a low oral bioavailability and/or short duration of action. Subcutaneous infusions allow for pulsatile, sustained and predictable delivery of the investigational agents in an ambulatory setting. The investigational agents will be combined into a 4 day infusion, and each infusion will have a total volume of 30mls. In total, each participant will receive 4 infusions with a break between the 2nd and 3rd infusions. There is no proposal for ongoing treatment.
Interventions
The proposed intervention is an open label, proof of concept trial with participants receiving subcutaneous infusions of a microdose combination of naltrexone / flumazenil. The investigational agents will be combined into an infusion, and each infusion will have a total volume of 30mls. Each patient will receive 4 infusions in total over the course of the trial. 22 days of treatment (4 x 96 hour subcutaneous infusions of combination naltrexone / flumazenil with a 6 day intermission) will occur.
The proposed intervention is an open label, proof of concept trial with participants receiving subcutaneous infusions of a microdose combination of naltrexone / flumazenil. The investigational agents will be combined into an infusion, and each infusion will have a total volume of 30mls. Each patient will receive 4 infusions in total over the course of the trial. 22 days of treatment (4 x 96 hour subcutaneous infusions of combination naltrexone / flumazenil with a 6 day intermission) will occur. Participants will be patients presenting to Currumbin Clinic as inpatients or outpatients primarily for treatment of major depressive disorder. Patients will be screened for eligibility and offered to participate in the study during an appointment with the chief investigator. The infusion apparatus will be a Springfusor device, 30ml, with flow rate limited tubing. A sterile 25 gauge butterfly needle will be inserted into the subcutaneous tissue of the abdomen for each infusion, using a clean technique. Fixomull with or without crepe bandages will be required to secure the infusion to the abdomen. No formal monitoring of adherence is possible due to the prolonged and continuous nature of the treatments, but disturbance of the infusion apparatus would be noticed when the investigator is changing or removing the infusion.
Sponsors
Trexapharm Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Major Depressive Disorder, with any current symptoms according to DSM criteria. There will be no inclusion criteria based on symptom range or severity. Treatment resistance defined as 3 (three) or more failed trials of antidepressant treatments of adequate dose and duration, which can include neurostimulation and/or completed structured psychotherapy.
Exclusion criteria
Patients will be excluded if they suffer hepatitis or hepatic failure, severe immunosuppression, multiple sclerosis, epilepsy or have a history of seizures, organ transplantation, are pregnant or are breastfeeding, take >5mg daily dose equivalent of Diazepam, are under 18 years of age or are unable or unwilling to provide informed consent.
Outcome results
None listed