Overview

Tofacitinib in Depression (TIDE)

Status:
Suspended
Trial end date:
2021-09-01
Target enrollment:
0
Participant gender:
All
Summary
This study will test whether 7-10 day administration of the anti-inflammatory drug, tofacitinib, has positive effects on people experiencing treatment-resistant depression compared to placebo.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University of Oxford
Collaborators:
Medical Research Council
Wellcome Trust
Treatments:
Tofacitinib
Criteria
Inclusion Criteria:

- Male or female;

- Aged 18-65 years;

- Willing and able to give informed consent for participation in the study;

- Sufficiently fluent English to understand and complete the tasks;

- Registered with a GP and consents to GP being informed of participation in the study;

- Participants need to meet a number of concurrent clinical criteria:

- Current criteria for Major Depressive Disorder [as determined by the Structured
Clinical interview for DSM-5 (SCID-5)];

- Inadequate response to at least two adequate courses of antidepressant therapy each
given at a therapeutic dose for at least four weeks;

- Baseline elevated inflammation [as determined by high-sensitivity C-reactive protein
(hs-CRP) of 1mg/L or greater [~70% of patients expected to be above (estimated from
Chamberlain-2018)];

- Participants engaging in sex with a risk of pregnancy must agree to use a highly
effective method of contraception from Screening Visit until 30 days after receiving
the study medication treatment. Acceptable methods of contraception include:

- Combined (estrogen- and progestogen-containing) hormonal contraception associated with
inhibition of ovulation: oral, intravaginal or transdermal;

- Progestogen-only hormonal contraception associated with inhibition of ovulation: oral,
injectable or implantable;

- Intrauterine device (IUD);

- Intrauterine hormone-releasing system (IUS);

- Bilateral tubal occlusion;

- Vasectomy (or vasectomised partner);

- Condoms +/- spermicides;

- Sexual abstinence. [Periodic abstinence (calendar, symptothermal, post-ovulation
methods), withdrawal (coitus interruptus), and spermicides only are not acceptable
methods of contraception.]

- Male participants must not donate sperm

Exclusion Criteria:

- History of /or current DSM-5 bipolar disorder or schizophrenia.

- Current DSM-5 eating disorder.

- Participants who fulfil current criteria for other comorbid disorders may still be
entered into the study, if, in the opinion of the Investigator, the psychiatric
diagnosis will not compromise safety or affect data quality;

- Participants currently taking strong cytochrome P450 (CYPs) 3A4 inhibitors (e.g.
fluvoxamine)

- Electroconvulsive therapy for the treatment of the current episode of depression;

- Clinically significant abnormal values for full blood count, urea and electrolytes,
liver function tests, blood pressure, or ECG. A participant with a clinical
abnormality or parameters outside the reference range for the population being studied
may be included only if the Investigator considers that the finding is unlikely to
introduce additional risk factors and will not interfere with the study procedures;

- Participants who are positive for blood-borne viruses (HIV/HepB/HepC);

- Participants who are positive to tuberculosis' screening test (T-SPOT.TB +);

- Participants receiving or planning to receive a live vaccine within 4 weeks of study
treatment; if the patient is due an influenza vaccine, this should be rescheduled to 2
weeks after the study.

- History of significant alcohol/substance misuse or dependence over the past 6 months;

- History of, or current medical conditions that in the opinion of the Investigator may
interfere with the safety of the participant or the scientific integrity of the study,
including recurrent infections (e.g. sinusitis, genital herpes simplex, or herpes
zoster), malignancies (except for successfully treated non-melanoma skin cancer or
localised carcinoma in situ of the cervix), severe neurological problems (e.g.
Parkinson's disease; blackouts requiring hospitalization, epilepsy/seizures, stroke,
other brain injury), severe cardiovascular disorder (e.g. moderate-severe congestive
heart failure, cerebrovascular accident, myocardial infarction, coronary stenting,
uncontrolled hypertension systolic >160 mmHg or diastolic >100 mmHg, unprovoked deep
vein thrombosis or pulmonary embolism), severe haematological disorder (e.g. total
white blood cell count <3,000/μL, absolute neutrophil count <1,500/μL, platelet count
<100,000/μL, absolute lymphocyte count <800/μL, hemoglobin <10 g/dL), severe hepatic
disease (e.g. serum alanine transaminase (ALT) >2 × upper limit of normal),
significant renal disease (e.g. estimated glomerular filtration rate (GFR) by
simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula > 40
mL/min/1.73m2), severe gastro-intestinal problems (e.g. diverticulitis, previous
perforation or high risk of perforation, conditions that could interfere with drug
absorption including but not limited to short bowel syndrome); previous organ
transplant;

- Clinically significant risk of suicide;

- Current pregnancy (as determined by urine pregnancy test taken during the Screening
Visit and the Research Visit One), breastfeeding, or planning a pregnancy during the
course of the study;

- Participants with Body Mass Index (BMI - kg/m2) outside the 18-36 range at Screening
Visit;

- Participants with severe claustrophobia;

- Participants with ferromagnetic objects in their bodies (e.g. metal implants, vessel
clips, shrapnel injuries) or with implanted devices which may be damaged by the magnet
(e.g. heart pacemakers);

- Previous participation in a study using the same, or similar, emotional or reward
processing tasks;

- Previous participation in a psychological or medical study involving the use of
medication within the last 3 months;

- Participant received non-prescription medication, including supplements such as
vitamins and herbal supplements within 48 hours prior to the Research Visit One (apart
from paracetamol). Participants who have taken non-prescription medication may still
be entered into the study, if, in the opinion of the Investigator, the medication
received will not interfere with the study procedures or compromise safety;

- Participant with a known hypersensitivity to tofacitinib;

- Participant with planned medical treatment within the study period that might
interfere with the study procedures;

- Participant who is unlikely to comply with the clinical study protocol or is
unsuitable for any other reason, in the opinion of the Investigator.