PF-04995274 and Emotional Processing in Un-medicated Depression

NCT03516604 | Completed Phase 1

• 2 other identifiers: PF04995274 Study 1 RESTANDMR/P012604/1
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test whether seven days administration of a serotonin receptor subtype 4 (5HT4) agonist called PF-04995274 has positive effects on cognition, emotional processing and neural activity in unmedicated depressed patients compared to placebo. The study will also include a group of patients randomised to seven days administration of citalopram (20 mg), which is a standard treatment for depression.

Conditions

Depression, Unipolar

Outcome Measures

Primary Outcomes (2)

• Hippocampal BOLD signal during fMRI

  Hippocampal and parahippocampal BOLD signal during familiar novel task - participants are presented with either previously trained (familiar) or novel images and are asked to identify whether animal or non-animal with a button press

  Completed on Day 6-8

• BOLD signal during fMRI

  Amygdala, anterior cingulate, prefrontal and orbitofrontal BOLD signal during emotional faces task - participants are presented with pictures of facial expressions of emotions and are asked to identify the gender of each face via button press.

  Completed on Day 6-8

Secondary Outcomes (4)

• Auditory Verbal Learning Task (AVLT)

  Completed on Day 7-9

• Emotional Memory Task

  Completed on Day 7-9

• Facial Expression Recognition Task (FERT)

  Completed on Day 7-9

• Probabilistic Instrumental Learning Task (PILT)

  Completed on Day 7-9

Study Arms (3)

PF-04995274

EXPERIMENTAL

PF-04995274, three x 5mg tablet (15mg total), once daily for 7-9 days \+ 1 placebo capsule, once daily for 7-9 days

Drug: PF-04995274; Drug: Placebo oral capsule

Citalopram

ACTIVE COMPARATOR

Citalopram, one x 20mg capsule, once daily for 7-9 days \+ 3 placebo tablets, once daily for 7-9 days

Drug: Citalopram; Drug: Placebo Oral Tablet

Placebo

PLACEBO COMPARATOR

3 placebo tablets and 1 placebo capsule, once daily for 7-9 days

Drug: Placebo Oral Tablet; Drug: Placebo oral capsule

Interventions

PF-04995274 DRUG

PF-04995274 tablets

PF-04995274

Citalopram DRUG

Citalopram capsule

Also known as: Celexa, Cipramil

Citalopram

Placebo Oral Tablet DRUG

Placebo tablet, identical to PF-04995274 tablet

Citalopram; Placebo

Placebo oral capsule DRUG

Placebo capsule, identical to citalopram capsule

PF-04995274; Placebo

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), 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 study;
• Meet DSM-V criteria for current Major Depressive Disorder \[as determined by the Structured Clinical interview for DSM-V (SCID)\];
• Participant must have received no drug or face-to-face psychological treatment for the current episode of depression/ in the previous six weeks;
• 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, female participants must not breastfeed, and male participants must not donate sperm.

You may not qualify if:

• 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;
• Current usage of psychotropic medication;
• Failure to respond to antidepressant medication in current episode;
• Electroconvulsive therapy for the treatment of the current episode of depression;
• 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; blackouts requiring hospitalisation);
• Medical conditions that may alter the hemodynamic parameters underlying the BOLD signal (e.g., inadequately treated hypertension, diabetes mellitus);
• 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 drug treatment;
• Any contraindication to MRI scanning (e.g. metal objects in body, pacemakers, significant claustrophobia, pregnancy);
• Participants with Body Mass Index (BMI) outside the 18 to 36 kg/m2 range at the Screening Visit.

Sponsors & Collaborators

• University of Oxford: lead
• Medical Research Council: collaborator
• Pfizer: collaborator

Study Sites (1)

University of Oxford

Oxford, Oxfordshire, OX3 7JX, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 32241310 DERIVED

MeSH Terms

Conditions

Depressive Disorder

Interventions

Citalopram; Dexetimide

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Catherine Harmer

  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: SPONSOR

Model Details: Participants will be randomly allocated to one of three groups (PF-04995264, citalopram or placebo) and receive their allocated study medication for 7 days.

Study Record Dates

• First Submitted: April 23, 2018
• First Posted: May 4, 2018
• Study Start: May 16, 2018
• Primary Completion: July 29, 2022
• Study Completion: July 29, 2022
• Last Updated: November 3, 2022

Record last verified: 2022-10

Locations

GB (1)