None listed
Conditions
Brief summary
Chronic inflammation is present in approximately one-third of individuals with depression, and may increase the likelihood of recurring episodes of depression and contribute to treatment resistance. Low-dose naltrexone (LDN) is a drug that appears to have unique anti-inflammatory effects in the brain, and has been shown to improve mood in a pilot trial in depression. This study aims to determine if LDN can equally help people with high and low levels of inflammation and depression. It is hypothesized that participants in the high inflammation group taking LDN will experience a greater reduction in symptoms, blood concentrations of inflammatory markers and magnetic resonance imaging markers of inflammation compared to the low-inflammation group and placebo groups. The results will shed light on the inflammatory processes contributing to MDD, symptoms and biomarkers associated with inflammation in depression, and the role of LDN as a treatment for patient groups for whom standard antidepressants are ineffective.
Interventions
The intervention, low-dose naltrexone (LDN), consists of 1.5 mg of naltrexone hydrochloride with microcrystalline cellulose (MCC) within a gelatine capsule shell. Participants in the durability arm will take 1 capsule orally once daily at night for 1 week, then 2 capsules at night for 1 week, then 3 capsules (4.5 mg) orally once daily at night for 10 weeks. This dosing schedule will be repeated again at 12 weeks, the beginning of the 12 week open-label extension, to maintain blinding. If partici
The intervention, low-dose naltrexone (LDN), consists of 1.5 mg of naltrexone hydrochloride with microcrystalline cellulose (MCC) within a gelatine capsule shell. Participants in the durability arm will take 1 capsule orally once daily at night for 1 week, then 2 capsules at night for 1 week, then 3 capsules (4.5 mg) orally once daily at night for 10 weeks. This dosing schedule will be repeated again at 12 weeks, the beginning of the 12 week open-label extension, to maintain blinding. If participants experience adverse effects, the dose may be titrated down to either 2 capsules daily or 1 capsule twice daily. An unblinded pharmacist independent of the study team will dispense the interventions to participants once a month. At the end of each month participants will return their capsule bottles, and the number of capsules left in the bottle will be used to calculate intervention compliance. Participants will be contacted by the study team after the day of medication delivery at 1 day, 3 days, 1 week, 2 weeks , 4 weeks, 8 weeks, 12 weeks, 13 weeks, 14 weeks, 16 weeks and 20 weeks to remind participants to adhere to study protocols and to check for adverse effects.
Sponsors
University of Auckland
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion criteria for participants with depression: - Provision of signed and dated informed consent form - Stated willingness to comply with all study procedures and availability for the duration of the study - Male or female, aged 18 to 55 years. - Diagnosis of MDD as per the Diagnostic and Statistical Manual 5 criteria for MDD - Experiencing significant depressive symptoms, as indicated by a score greater than or equal to 18 on the MADRS - Receiving treatment with an antidepressant agent (not greater than Stage II antidepressant resistance as defined by the Thase and Rush treatment-resistant depression staging method) - Clinically stable for at least four weeks - hsCRP levels either greater than or equal to 3 mg/L, or less than or equal to 1 mg/L - Ability to take oral medication and be willing to adhere to the dosing regimen - Agreement to adhere to Lifestyle Considerations throughout study duration (participants will be asked to abstain from alcohol and drugs for 24 hours before the start of each MRI and EEG session, and have a plan with their doctor to stay on the same antidepressant for at least 12 weeks). Inclusion criteria for healthy controls: - Provision of signed and dated informed consent form - Stated willingness to comply with all study procedures and availability for the duration of the study - Male or female aged 18 to 55 years -hsCRP levels less than or equal to 1 mg/L - Agreement to adhere to Lifestyle Considerations throughout study duration (healthy participants will be asked to abstain from alcohol and drugs for 24 hours before the start of each MRI and EEG session)
Exclusion criteria
Exclusion criteria for participants with depression: - Current use of prescription opioid analgesics, psychostimulants, dopamine agonists - Current use of any opioid-based drugs recreationally - Any current or past bipolar or psychiatric disorder or psychotic features (other psychiatric conditions such as anxiety will be allowed for individuals with MDD, provided they are not the primary source of the participant’s depressive symptomatology) - Acute risk of suicide - Any known neurological disorders or neurodegenerative condition - Acute infectious pathology, or chronic or acute inflammatory diseases that, in the judgement of the investigators, interferes with study measures or procedures - Any clinically significant medical conditions, e.g., renal, hepatic, or cardiovascular conditions, uncontrolled thyroid dysfunction, metabolic disorders, cancer, seizure disorders - Uncontrolled autoimmune diseases or severe chronic pain - Or any other condition that, in the judgement of the investigators, interferes with study measures or procedures - Long-term, frequent, anti-inflammatory or immunosuppressive therapy - Contraindications to MRI or blood tests, including those who refuse to be informed of an incidental finding - Women who are pregnant or breastfeeding, or women of child-bearing age who are not on a medically acceptable form of contraception - Substance use disorders within the previous 12 months - Any allergy or intolerance to naltrexone Exclusion criteria for healthy controls: - Current use of any medication other than contraception - Current use of any opioid-based drugs recreationally - Any current or past psychiatric conditions - Any known neurological disorders or neurodegenerative condition - Acute infectious pathology, or chronic or acute inflammatory diseases - Any clinically significant medical conditions, e.g., renal, hepatic, or cardiovascular conditions, uncontrolled thyroid dysfunction, metabolic disorders, history of cancer, seizure disorders - Autoimmune diseases or chronic pain - Long-term anti-inflammatory or immunosuppressive therapy - Contra-indications to MRI or blood tests, including those who refuse to be informed of an incidental finding. - Women who are on hormone suppressants. - Women who are pregnant or breastfeeding
Outcome results
None listed