Tofacitinib in Depression (TIDE)

NCT04141904 | Terminated Phase 1

• 1 other identifier: 19/SC/0136
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Depression; Inflammation

Keywords

Depression

Outcome Measures

Primary Outcomes (1)

• The effects of tofacitinib on emotional processing using the Facial Expression Recognition Task (FERT)

  Accuracy and reaction times on computer-based tasks of emotional processing using facial expressions of basic emotions (happiness, fear, anger, disgust, sadness, surprise) are displayed on the screen and participants are asked to correctly classify them. Each emotion is presented at different intensity levels. Responses are made via a button-press and accuracy and reaction time are recorded

  Day 7-10 of drug/placebo administration

Secondary Outcomes (8)

• The effects of tofacitinib on Emotional Memory Task (EMEM) scores

  Day 7-10 of drug/placebo administration

• Emotional categorization using the Emotional categorization task (ECAT)

  Day 7-10 of drug/placebo administration

• Emotional recall task (EREC)

  Day 7-10 of drug/placebo administration

• Brain neural activity

  Day 7-10 of drug/placebo administration

• Faces dot probe task (FDOT)

  Day 7-10 of drug/placebo administration

Study Arms (2)

Tofacitinib

EXPERIMENTAL

Tofacitinib 5mg capsule twice a day for 7-10 days

Drug: Tofacitinib 5 MG [Xeljanz]

Placebo

PLACEBO COMPARATOR

Placebo capsule twice a day for 7-10 days

Other: Placebo

Interventions

Tofacitinib 5 MG [Xeljanz] DRUG

Tofacitinib 5mg capsules twice a day for 7-10 days

Tofacitinib

Placebo OTHER

Placebo capsules twice a day for 7-10 days

Placebo

Eligibility Criteria

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

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• University of Oxford: lead
• Wellcome Trust: collaborator
• Medical Research Council: collaborator

Study Sites (1)

Department of Psychiatry, University of Oxford

Oxford, Oxfordshire, OX3 7JX, United Kingdom

Location

MeSH Terms

Conditions

Depression; Inflammation

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Philip J Cowen

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants will be randomly allocated to one of two groups (tofacitinib or placebo) and take the assigned medication for 7-10 days

Study Record Dates

• First Submitted: October 14, 2019
• First Posted: October 28, 2019
• Study Start: February 10, 2020
• Primary Completion: May 23, 2022
• Study Completion: May 23, 2022
• Last Updated: August 9, 2022

Record last verified: 2022-08

Locations

GB (1)