ClinicalTrials.gov
ClinicalTrials.gov Menu

PF-04995274 and Emotional Processing in Un-medicated Depression (RESTAND)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03516604
Recruitment Status : Recruiting
First Posted : May 4, 2018
Last Update Posted : July 4, 2018
Sponsor:
Collaborators:
Medical Research Council
Pfizer
Information provided by (Responsible Party):
University of Oxford

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 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.

Condition or disease Intervention/treatment Phase
Depression, Unipolar Drug: PF-04995274 Drug: Citalopram Drug: Placebo Oral Tablet Drug: Placebo oral capsule Phase 1

Detailed Description:
This study uses a double-blind, placebo-controlled, randomised between-groups design to test if administration of a serotonin receptor subtype 4 (5HT4) agonist called PF-04995274 has positive effects on emotional processing and neural activity in unmedicated depressed patients. Participants are patients who fulfill criteria for current episode of Major Depressive Disorder (MDD), and they will be randomised to receive 7 days treatment with either PF-04995274 (15 mg daily), citalopram (20 mg daily) or a matched placebo. Participants will come for a Screening Visit, a First Dose Visit, Research Visit One (including MRI scan) and Research Visit Two (including measures of emotional processing and non-emotion cognition).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will be randomly allocated to one of three groups (PF-04995264, citalopram or placebo) and receive their allocated study medication for 7 days.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Effects of PF-04995274 on Emotional Processing in Un-medicated Depressed Patients
Actual Study Start Date : May 16, 2018
Estimated Primary Completion Date : April 30, 2020
Estimated Study Completion Date : April 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PF-04995274

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
PF-04995274 tablets

Drug: Placebo oral capsule
Placebo capsule, identical to citalopram capsule

Active Comparator: Citalopram

Citalopram, one x 20mg capsule, once daily for 7-9 days

+ 3 placebo tablets, once daily for 7-9 days

Drug: Citalopram
Citalopram capsule
Other Name: Celexa, Cipramil

Drug: Placebo Oral Tablet
Placebo tablet, identical to PF-04995274 tablet

Placebo Comparator: Placebo
3 placebo tablets and 1 placebo capsule, once daily for 7-9 days
Drug: Placebo Oral Tablet
Placebo tablet, identical to PF-04995274 tablet

Drug: Placebo oral capsule
Placebo capsule, identical to citalopram capsule




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Amygdala BOLD signal during fMRI [ Time Frame: Completed on Day 6 ]
    Amygdala 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.

  2. Emotional Memory Task [ Time Frame: Completed on Day 7 ]
    Recall and recognition of affective words displayed earlier in the testing session is tested

  3. Auditory Verbal Learning Task (AVLT) [ Time Frame: Completed on Day 7 ]
    Accuracy of recall on the auditory verbal learning task

  4. Hippocampal BOLD signal during fMRI [ Time Frame: Completed on Day 6 ]
    Hippocampal 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

  5. Probabilistic Instrumental Learning Task (PILT) [ Time Frame: Completed on Day 7 ]
    Participants have to learn which shapes are associated with wins and losses and sensitivity to reward is assessed.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   16 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

Exclusion Criteria:

  • 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.
  • 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 Visit 2 (apart from 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 Visit 2 (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, citalopram 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03516604


Contacts
Contact: Amy Gillespie 01865 618324 amy.gillespie@psych.ox.ac.uk
Contact: Wendy Howard 01865 618286 wendy.howard@psych.ox.ac.uk

Locations
United Kingdom
University of Oxford Recruiting
Oxford, Oxfordshire, United Kingdom, OX3 7JX
Contact: Amy Gillespie       amy.gillespie@psych.ox.ac.uk   
Principal Investigator: Catherine Harmer, PhD         
Sub-Investigator: Philip Cowen, MD         
Sponsors and Collaborators
University of Oxford
Medical Research Council
Pfizer
Investigators
Principal Investigator: Catherine Harmer University of Oxford
  Study Documents (Full-Text)

Documents provided by University of Oxford:
Informed Consent Form  [PDF] February 21, 2018


Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT03516604     History of Changes
Other Study ID Numbers: PF04995274 Study 1 RESTAND
MR/P012604/1 ( Other Grant/Funding Number: MRC (UK) )
First Posted: May 4, 2018    Key Record Dates
Last Update Posted: July 4, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Citalopram
Dexetimide
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents