DepressionPhase 1/2TIDENCT04141904
Tofacitinib in Depression (TIDE)
A Phase 1/2 study testing Tofacitinib 5 MG [Xeljanz] in people with Depression and Inflammation, run by University of Oxford at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Depression, Inflammation
- What is being tested?
- Tofacitinib 5 MG [Xeljanz]
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 10 Feb 2020to 23 May 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Department of Psychiatry, University of Oxford
Oxford, Oxfordshire, OX3 7JX
About this study
Official title: The Effects of the Anti-inflammatory Drug, Tofacitinib on Emotional and Reward Processing in Patients With Treatment-resistant Depression and Elevated High-sensitivity C-reactive Protein
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.
Read the detailed description
This study uses a double-blind, placebo-controlled, randomised between groups design to test the hypothesis that, compared to placebo, 7-10 days' administration of tofacitinib 5mg twice daily has positive effects on emotional and reward processing in patients with treatment-resistant depression (TRD) and elevated C-reactive protein (hs-CRP; a marker of inflammation). Patients will have been diagnosed with Major Depressive Disorder using the Structured Clinical Interview for DSM-5 and will have shown non-response to at least 2 adequate antidepressant trials.They will also have a plasma hs-CRP of 1mg/L or greater. During the study patients will continue their antidepressant treatment. Participants will be randomised to receive 7-10 days treatment with either tofacitinib 5 mg twice daily or a matched placebo. This study includes three visits in total: a screening visit; research visit 1 (includes cognitive tests) and research visit 2 (to include an MRI scan as well as cognitive tests).
- Conditions
- Depression, Inflammation
- Being tested
- Tofacitinib 5 MG [Xeljanz], Placebo
- Keywords
- Depression
- Medical subject headings
- Depression, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tofacitinib 5 MG [Xeljanz]Drug
Tofacitinib 5mg capsules twice a day for 7-10 days
PlaceboOther
Placebo capsules twice a day for 7-10 days
| Study group | Role | What they receive |
|---|---|---|
| Tofacitinib | Experimental | Tofacitinib 5mg capsule twice a day for 7-10 days Receives: Drug: Tofacitinib 5 MG [Xeljanz] |
| Placebo | Placebo comparator | Placebo capsule twice a day for 7-10 days Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Day 7-10 of drug/placebo administration
Secondary outcomes (8)
The effects of tofacitinib on Emotional Memory Task (EMEM) scores
Recall and recognition of affective words displayed earlier in the testing session is tested
Measured: Day 7-10 of drug/placebo administration
Emotional categorization using the Emotional categorization task (ECAT)
Disagreeable or agreeable personality descriptions are presented and participants are asked to indicate whether they would like or dislike to be described as each of these characteristics. Responses are made via a button-press.
Measured: Day 7-10 of drug/placebo administration
Emotional recall task (EREC)
Participants are asked to write down as many of the words as they can remember from the previous task. Responses are made via pencil and paper.
Measured: Day 7-10 of drug/placebo administration
Brain neural activity
BOLD fMRI at resting state and during the performance of an emotional (i.e. covert facial expression processing) and a reward (i.e. adapted probabilistic instrumental learning) processing tasks.
Measured: Day 7-10 of drug/placebo administration
Faces dot probe task (FDOT)
Participants carry out computer-based tasks and attentional vigilance to happy or fearful faces is recorded from participants' response latency to indicate the alignment of a dot probe appearing in the place of one of the faces
Measured: Day 7-10 of drug/placebo administration
Probabilistic Instrumental Learning Task (PILT)
Participants have to learn which shapes are associated with wins and losses and sensitivity to reward is measured.
Measured: Day 7-10 of drug/placebo administration
Auditory Verbal Learning Task (AVLT)
Accuracy of recall on the auditory verbal learning task
Measured: Day 7-10 of drug/placebo administration
The effects of tofacitinib on cerebral perfusion
Arterial spin labelling at rest to measure cerebral perfusion
Measured: Day 7-10 of drug/placebo administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2019
- Study start10 Feb 2020
- Primary completion23 May 2022
- Study completion23 May 2022
Why it stopped: Covid-19 pandemic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomly allocated to one of two groups (tofacitinib or placebo) and take the assigned medication for 7-10 days
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Wellcome Trust, Medical Research Council
- Responsible party
- Principal investigator, Philip John Cowen, University of Oxford
- Investigators
- Philip J Cowen, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04141904
- Sponsor's protocol ID
- 19/SC/0136
- Acronym
- TIDE
- Status last verified
- Aug 2022
- First submitted
- 14 Oct 2019
- Last updated
- 9 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of the Anti-inflammatory Drug, Tofacitinib on Emotional and Reward Processing in Patients With Treatment-resistant Depression and Elevated High-sensitivity C-reactive Protein
- ClinicalTrials.gov ID
- NCT04141904
- Acronym / sponsor ID
- TIDE / 19/SC/0136
- Conditions
- Depression, Inflammation
- Keywords
- Depression
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Covid-19 pandemic
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Wellcome Trust, Medical Research Council
- Study start
- 10 Feb 2020 (actual)
- Primary completion
- 23 May 2022 (actual)
- Study completion
- 23 May 2022 (actual)
- First posted
- 28 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study uses a double-blind, placebo-controlled, randomised between groups design to test the hypothesis that, compared to placebo, 7-10 days' administration of tofacitinib 5mg twice daily has positive effects on emotional and reward processing in patients with treatment-resistant depression (TRD) and elevated C-reactive protein (hs-CRP; a marker of inflammation). Patients will have been diagnosed with Major Depressive Disorder using the Structured Clinical Interview for DSM-5 and will have shown non-response to at least 2 adequate antidepressant trials.They will also have a plasma hs-CRP of 1mg/L or greater. During the study patients will continue their antidepressant treatment. Participants will be randomised to receive 7-10 days treatment with either tofacitinib 5 mg twice daily or a matched placebo. This study includes three visits in total: a screening visit; research visit 1 (includes cognitive tests) and research visit 2 (to include an MRI scan as well as cognitive tests).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomly allocated to one of two groups (tofacitinib or placebo) and take the assigned medication for 7-10 days
| Arm | Type | Receives |
|---|---|---|
| Tofacitinib | Experimental | Drug: Tofacitinib 5 MG [Xeljanz]Tofacitinib 5mg capsule twice a day for 7-10 days |
| Placebo | Placebo comparator | Other: PlaceboPlacebo capsule twice a day for 7-10 days |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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;
Key exclusion criteria (22 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tofacitinib 5 MG [Xeljanz]Tofacitinib 5mg capsules twice a day for 7-10 days | Drug | Tofacitinib |
| PlaceboPlacebo capsules twice a day for 7-10 days | Other | Placebo |
Primary outcome
The effects of tofacitinib on emotional processing using the Facial Expression Recognition Task (FERT)
Time frame: Day 7-10 of drug/placebo administration
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
8 secondary outcomes
The effects of tofacitinib on Emotional Memory Task (EMEM) scores
Time frame: Day 7-10 of drug/placebo administration
Emotional categorization using the Emotional categorization task (ECAT)
Time frame: Day 7-10 of drug/placebo administration
Emotional recall task (EREC)
Time frame: Day 7-10 of drug/placebo administration
Brain neural activity
Time frame: Day 7-10 of drug/placebo administration
Faces dot probe task (FDOT)
Time frame: Day 7-10 of drug/placebo administration
Probabilistic Instrumental Learning Task (PILT)
Time frame: Day 7-10 of drug/placebo administration
Auditory Verbal Learning Task (AVLT)
Time frame: Day 7-10 of drug/placebo administration
The effects of tofacitinib on cerebral perfusion
Time frame: Day 7-10 of drug/placebo administration
Results and safety
The study was stopped early (reason given: Covid-19 pandemic). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philip J Cowen principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tofacitinib 5 MG [Xeljanz] in people with Depression and Inflammation, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Covid-19 pandemic). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The effects of tofacitinib on emotional processing using the Facial Expression Recognition Task (FERT) (time frame: Day 7-10 of drug/placebo administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2022.