Depression, UnipolarPhase 1RESTARTNCT03515733
PF-04995274 and Emotional Processing in Treatment Resistant Depression
A Phase 1 study testing PF-04995274 in people with Depression, Unipolar and Treatment Resistant Depression, run by University of Oxford at 1 site in United Kingdom.
Trial summary
This study will test whether seven days adjunctive administration of a serotonin receptor subtype 4 (5HT4) agonist called PF-04995274 has positive effects on emotional processing and non-emotional cognition in medicated, treatment-resistant depressed patients compared to placebo. Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Depression, Unipolar, Treatment Resistant Depression
- What is being tested?
- PF-04995274
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 31 May 2018to 26 Jul 2022
- Phase
- Phase 1
- 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 16 to 65 years
- All sexes
- No healthy volunteers
- Child, 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 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-V (SCID)];
- Failure within the current depressive episode to respond clinically to at least one course of antidepressant therapy, each given at a therapeutic dose for at least four weeks [as determined by use of the MGH Antidepressant Treatment Response Questionnaire (ATRQ)];
- Currently taking an antidepressant, which must be either a Selective Serotonin Reuptake Inhibitor (SSRI) - with the exception of fluoxetine, paroxetine or fluvoxamine - or a Serotonin-norepinephrine reuptake inhibitor (SNRI) ; Participants currently taking excluded medications can be switched to sertraline or citalopram;
- 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 study medication treatment, and male participants must not donate sperm.
Who cannot join
- History of or current DSM-V bipolar disorder, schizophrenia or eating disorders. 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;
- First-degree relative with a diagnosis of Bipolar Disorder type 1;
- Participants currently taking strong cytochrome P450 (CYPs) enzymes inhibitors, such as fluoxetine, paroxetine or fluvoxamine (in order to avoid drug-drug interactions);
- Participants currently taking psychotropic medications which in the opinion of the investigator may interfere with the safety of the participant or the scientific integrity of the study;
- Participants who have previously failed a combination/augmentation therapy (i.e., therapy with the combination of two or more pharmacological agents) for the treatment of depression, which in the opinion of the Investigator may reduce the likelihood of responding;
- Electroconvulsive therapy for the treatment of the current episode of depression;
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- Participants undergoing any form of face-to-face structured psychological treatment during the study;
- Clinically significant abnormal values for liver function tests, clinical chemistry, urine drug screen, blood pressure measurement and 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;
- History of stimulant abuse (lifetime; e.g. amphetamine, cocaine), or of alcohol abuse within one year or of alcohol dependence within the lifetime;
- History of, or current medical conditions which in the opinion of the investigator may interfere with the safety of the participant or the scientific integrity of the study, including epilepsy/seizures, brain injury, severe hepatic or renal disease, severe gastro-intestinal problems, Central Nervous System (CNS) tumors, severe neurological problems (like Parkinson's Disease; blackouts requiring hospitalisation);
- Clinically significant risk of suicide;
- Current pregnancy (as determined by urine pregnancy test taken during Screening and First Dose Visits), breastfeeding or planning a pregnancy during the course of the study;
- Participant not willing to use a suitable method of contraception for 30 days after receiving study medication treatment;
- Participants with Body Mass Index (BMI - kg/m2) outside the 18 - 36 range at the Screening Visit;
- Night-shift working or recent travel involving significant change of timezones;
- Excessive caffeine consumption, i.e., consumption higher than 8 cups of standard caffeinated drinks (tea, instant coffee) or higher than 6 cups of stronger coffee or other drinks containing methylxanthines such as coca cola or Red Bull per day;
- Participation in a psychological or medical study involving the use of medication within the last 3 months;
- Previous participation in a study using the same, or similar, emotional processing tasks;
- Smoker > 10 cigarettes per day or similar levels of tobacco consumption in other forms.
- Participant received prescribed medication within 28 days prior to First Dose Visit (apart from their prescribed antidepressant and the contraceptive pill). Participants who have taken 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 received non-prescription medication, including supplements such as vitamins and herbal supplements within 48 hours prior to First Dose Visit (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 PF-04995274 or any other serotonergic agents;
- 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.
About this study
Official title: The Effects of PF-04995274 on Emotional Processing in Treatment-resistant, Medicated, Depressed Patients
This study will test whether seven days adjunctive administration of a serotonin receptor subtype 4 (5HT4) agonist called PF-04995274 has positive effects on emotional processing and non-emotional cognition in medicated, treatment-resistant depressed patients compared to placebo.
Read the detailed description
This study uses a double-blind, placebo-controlled, randomised between-groups design to test if adjunctive administration of a serotonin receptor subtype 4 (5HT4) agonist called PF-04995274 has positive effects on emotional processing and neural activity in medicated treatment-resistant depressed patients. Participants are patients who fulfill criteria for current episode of Major Depressive Disorder (MDD) and have shown lack of response to antidepressant treatment, and they will be randomised to receive 7 days treatment with either PF-04995274 (15 mg daily) or a matched placebo. Participants will come for a Screening Visit, a First Dose Visit, and a Research Visit (including measures of emotional processing and non-emotion cognition).
- Being tested
- PF-04995274, Placebo Oral Tablet
- Medical subject headings
- Depressive Disorder, Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-04995274Drug
PF-04995274 tablets
Placebo Oral TabletDrug
Placebo tablet, identical appearance to experimental tablet
| Study group | Role | What they receive |
|---|---|---|
| PF-04995274 | Experimental | PF-04995274, three x 5mg tablet (15mg total), once daily for 7-9 days Receives: Drug: PF-04995274 |
| Placebo | Placebo comparator | 3 placebo tablets, once daily for 7-9 days Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Facial Expression Recognition Task (FERT)
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: Completed on Day 7
Auditory Verbal Learning Task (AVLT)
Accuracy of recall on the auditory verbal learning task
Measured: Completed on Day 7
Secondary outcomes (2)
Emotional Memory Task
Recall and recognition of affective words displayed earlier in the testing session is tested
Measured: Completed on Day 7
Probabilistic Instrumental Learning Task (PILT)
Participants have to learn which shapes are associated with wins and losses and sensitivity to reward is assessed.
Measured: Completed on Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2018
- Study start31 May 2018
- Primary completion26 Jul 2022
- Study completion26 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Depression, UnipolarStudies 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
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomly allocated to one of two groups (PF-04995264 or placebo) and receive their allocated study medication for 7 days.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Catherine Harmer, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03515733
- Sponsor's protocol ID
- PF04995274 Study 2 RESTART
- Acronym
- RESTART
- Status last verified
- Jul 2022
- First submitted
- 23 Apr 2018
- Last updated
- 4 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Murphy SE, de Cates AN, Gillespie AL, Godlewska BR, Scaife JC, Wright LC, Cowen PJ, Harmer CJ. Translating the promise of 5HT4 receptor agonists for the treatment of depression. Psychol Med. 2021 May;51(7):1111-1120. doi: 10.1017/S0033291720000604. Epub 2020 Apr 3.
PubMed 32241310
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of PF-04995274 on Emotional Processing in Treatment-resistant, Medicated, Depressed Patients
- ClinicalTrials.gov ID
- NCT03515733
- Acronym / sponsor ID
- RESTART / PF04995274 Study 2 RESTART
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 31 May 2018 (actual)
- Primary completion
- 26 Jul 2022 (actual)
- Study completion
- 26 Jul 2022 (actual)
- First posted
- 4 May 2018 (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 seven days adjunctive administration of a serotonin receptor subtype 4 (5HT4) agonist called PF-04995274 has positive effects on emotional processing and non-emotional cognition in medicated, treatment-resistant depressed patients compared to placebo.
Detailed description
This study uses a double-blind, placebo-controlled, randomised between-groups design to test if adjunctive administration of a serotonin receptor subtype 4 (5HT4) agonist called PF-04995274 has positive effects on emotional processing and neural activity in medicated treatment-resistant depressed patients. Participants are patients who fulfill criteria for current episode of Major Depressive Disorder (MDD) and have shown lack of response to antidepressant treatment, and they will be randomised to receive 7 days treatment with either PF-04995274 (15 mg daily) or a matched placebo. Participants will come for a Screening Visit, a First Dose Visit, and a Research Visit (including measures of emotional processing and non-emotion cognition).
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 (PF-04995264 or placebo) and receive their allocated study medication for 7 days.
| Arm | Type | Receives |
|---|---|---|
| PF-04995274 | Experimental | Drug: PF-04995274PF-04995274, three x 5mg tablet (15mg total), once daily for 7-9 days |
| Placebo | Placebo comparator | Drug: Placebo Oral Tablet3 placebo tablets, once daily for 7-9 days |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 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 study;
Key exclusion criteria (24 listed)
- History of or current DSM-V bipolar disorder, schizophrenia or eating disorders. 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;
- First-degree relative with a diagnosis of Bipolar Disorder type 1;
- Participants currently taking strong cytochrome P450 (CYPs) enzymes inhibitors, such as fluoxetine, paroxetine or fluvoxamine (in order to avoid drug-drug interactions);
- Participants currently taking psychotropic medications which in the opinion of the investigator may interfere with the safety of the participant or the scientific integrity of the study;
- Participants who have previously failed a combination/augmentation therapy (i.e., therapy with the combination of two or more pharmacological agents) for the treatment of depression, which in the opinion of the Investigator may reduce the likelihood of responding;
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 |
|---|---|---|
| PF-04995274PF-04995274 tablets | Drug | PF-04995274 |
| Placebo Oral TabletPlacebo tablet, identical appearance to experimental tablet | Drug | Placebo |
Primary outcome
Facial Expression Recognition Task (FERT)
Time frame: Completed on Day 7
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.
Auditory Verbal Learning Task (AVLT)
Time frame: Completed on Day 7
Accuracy of recall on the auditory verbal learning task
2 secondary outcomes
Emotional Memory Task
Time frame: Completed on Day 7
Probabilistic Instrumental Learning Task (PILT)
Time frame: Completed on Day 7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2022.
- Derived from this study: PubMed 32241310Murphy SE, de Cates AN, Gillespie AL, Godlewska BR, Scaife JC, Wright LC, Cowen PJ, Harmer CJ. Translating the promise of 5HT4 receptor agonists for the treatment of depression. Psychol Med. 2021 May;51(7):1111-1120. doi: 10.1017/S0033291720000604. Epub 2020 Apr 3.
- 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.
Catherine Harmer 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 study testing PF-04995274 in people with Depression, Unipolar and Treatment Resistant Depression, 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 10 inclusion and 24 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: finished, as of the sponsor's last update on 4 Nov 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 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.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Facial Expression Recognition Task (FERT) (time frame: Completed on Day 7). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03515733, which also lists 1 linked publication.
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 4 Nov 2022.