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Prucalopride and Cognition in Recovered Depression (PROGRESS)

Primary Purpose

Depression in Remission

Status
Recruiting
Phase
Early Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Prucalopride
Placebo
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Depression in Remission focused on measuring Cognition, Emotional processing

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Participant is willing and able to give informed consent for participation in the research
  • Male or female
  • Body mass index in the range of 18 to 33
  • Not currently taking any medications (except for contraception), including being antidepressant free for at least three months
  • Have at least two previous episodes of depression, and have been recovered from the most recent episode of depression for six months
  • Current PHQ-9 score < 10 (the cut off for DSM major depression)

Exclusion Criteria:

The participant may not enter the study if ANY of the following apply:

  • Any current Axis 1 DSM-5 psychiatric disorder
  • Any previous episode of a severe mental illness, other than Depressive Disorder. Comorbid Anxiety disorders will be allowed, but not OCD (Obsessive Compulsive Disorder) or PTSD.
  • A first degree relative diagnosed with Bipolar Affective Disorder Type 1 or Schizophrenia
  • Body Mass Index outside the range of 18 to 33 inclusive
  • Any significant current medical condition likely to interfere with conduct of the study or analysis of data
  • Current use of psychoactive and / or medically significant medication as judged by a study medic, whether prescribed or bought over the counter (the contraceptive pill, the Depo-Provera injection or the progesterone implant will not result in exclusion)
  • Ongoing psychopharmacological treatment for depression, including hypnotics (psychotherapy will be allowed as long as not newly-started in the last 6 weeks)
  • High consumption of licit substances to an extent that would make complying with study protocol challenging (including alcohol, caffeine, nicotine)
  • Past history of dependence to illicit substances, and any consumption of illicit substances in the three months prior to the study
  • Currently pregnant or breast feeding
  • Current, or a significant history of, gastro-intestinal disorder or irritable bowel syndrome
  • Known lactase deficiency or any other problem absorbing lactose, galactose, or glucose
  • Participation in a study that involves the use of a medication or novel vaccine within the last three months
  • Participation in a study using the same tasks in the last two years
  • Any physical (including visual and auditory) or language impairment that would make complying with the study protocol challenging

Sites / Locations

  • Department of Psychiatry, Warneford Hospital, University of OxfordRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Prucalopride

Placebo

Arm Description

Prucalopride - 1mg for 2 days, and then increased to 2mg for a further 5-8 days. Testing will occur on day 7 ideally, but may take place up to and including day 10.

Placebo (sucrose / lactose) for 7-10 days

Outcomes

Primary Outcome Measures

Performance (accuracy) across cognitive battery
To investigate the pattern of effects of sub-acute administration of 2mg prucalopride versus placebo on a battery of cognitive measures including attention (DSST), memory (AVLT), executive function (TMT-A/B), working memory (N-back), and reward sensitivity (PILT).

Secondary Outcome Measures

FERT
Accuracy (%) and reaction times on computer-based task of facial expression recognition (FERT), comparing those receiving drug and placebo.
ECAT/EREC/EMEM
Number of positive and negative words correctly categorised, recalled, and recognised on emotional memory task, comparing those receiving drug and placebo.
FDOT
Reaction times to fearful, happy, and neutral faces in masked and unmasked conditions (FDOT), comparing those receiving drug and placebo.
Emotional go/no-go
Reaction time and accuracy, comparing those receiving drug and placebo.
PDQ-20
Change of score from baseline, comparing those receiving drug and placebo.

Full Information

First Posted
January 25, 2022
Last Updated
January 25, 2022
Sponsor
University of Oxford
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1. Study Identification

Unique Protocol Identification Number
NCT05220228
Brief Title
Prucalopride and Cognition in Recovered Depression
Acronym
PROGRESS
Official Title
The Effect of 2mg Sub-acute Prucalopride on Cognition and Emotional Processing in Participants Recovered From Depression
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 4, 2022 (Actual)
Primary Completion Date
June 2023 (Anticipated)
Study Completion Date
June 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The current study has two aims: To test the effect of 5-HT4 receptor agonism on cognition (including memory, attention and cognitive control) in individuals with previous history of depression. To explore if prucalopride has an effect on emotional processing biases consistent with its effects on serotonin.
Detailed Description
Cognitive impairment within depression is common and appears to be at least partly separate from the mood component. It is not well targeted by current treatments and it may persist even after remission of mood symptoms. Therefore, it may be clinically beneficial to search for new therapies that are able to improve cognition in those who have, or are recovering from, depression. Agonists of the serotonin receptor subtype 4 (5-HT4) have shown two profiles of effect in animal models: (i) a pro-cognitive profile, improving in learning and memory on a range of rodent paradigms; and (ii) an antidepressant-like profile, reducing depression and anxiety-related behaviours in rodent models of depression and anxiety. A previous study in our group examining acute prucalopride administration (1mg) in 40 healthy human volunteers found improvements in learning and memory but little effect on emotional processing. This pro-cognitive effect was supported by a subsequent study where healthy volunteers received 7 days of prucalopride. In this study, prucalopride led to both better performance on a visual memory task, and increased activation in the hippocampus and an associated memory processing region in response to a memory stimulus. As short-term treatment with clinically-effective antidepressants such as SSRIs is known to produce positive biases in the processing of emotional information in healthy volunteers, this lack of effect on emotional processing was not consistent with prucalopride having antidepressant potential, and is surprising considering the strength of the animal data. One factor that has not yet been explored is whether the translation was limited due to the low dose of prucalopride used in our previous study. Therefore, we wish to see if we (i) can translate this pro-cognitive effect of prucalopride into participants with a previous history of depression and current mild cognitive issues; and (ii) can use a full treatment dose of prucalopride to evaluate its effect on emotional processing.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression in Remission
Keywords
Cognition, Emotional processing

7. Study Design

Primary Purpose
Other
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Prucalopride
Arm Type
Experimental
Arm Description
Prucalopride - 1mg for 2 days, and then increased to 2mg for a further 5-8 days. Testing will occur on day 7 ideally, but may take place up to and including day 10.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo (sucrose / lactose) for 7-10 days
Intervention Type
Drug
Intervention Name(s)
Prucalopride
Other Intervention Name(s)
Resolor, Montegrity, Axunio
Intervention Description
1mg prucalopride x 2d, 2mg prucalopride x 5-8d
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Lactose / sucrose placebo
Primary Outcome Measure Information:
Title
Performance (accuracy) across cognitive battery
Description
To investigate the pattern of effects of sub-acute administration of 2mg prucalopride versus placebo on a battery of cognitive measures including attention (DSST), memory (AVLT), executive function (TMT-A/B), working memory (N-back), and reward sensitivity (PILT).
Time Frame
Day 7-10
Secondary Outcome Measure Information:
Title
FERT
Description
Accuracy (%) and reaction times on computer-based task of facial expression recognition (FERT), comparing those receiving drug and placebo.
Time Frame
D7-10
Title
ECAT/EREC/EMEM
Description
Number of positive and negative words correctly categorised, recalled, and recognised on emotional memory task, comparing those receiving drug and placebo.
Time Frame
D7-10
Title
FDOT
Description
Reaction times to fearful, happy, and neutral faces in masked and unmasked conditions (FDOT), comparing those receiving drug and placebo.
Time Frame
D7-10
Title
Emotional go/no-go
Description
Reaction time and accuracy, comparing those receiving drug and placebo.
Time Frame
D7-10
Title
PDQ-20
Description
Change of score from baseline, comparing those receiving drug and placebo.
Time Frame
D7-10

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Participant is willing and able to give informed consent for participation in the research Male or female Body mass index in the range of 18 to 33 Not currently taking any medications (except for contraception), including being antidepressant free for at least three months Have at least two previous episodes of depression, and have been recovered from the most recent episode of depression for six months Current PHQ-9 score < 10 (the cut off for DSM major depression) Exclusion Criteria: The participant may not enter the study if ANY of the following apply: Any current Axis 1 DSM-5 psychiatric disorder Any previous episode of a severe mental illness, other than Depressive Disorder. Comorbid Anxiety disorders will be allowed, but not OCD (Obsessive Compulsive Disorder) or PTSD. A first degree relative diagnosed with Bipolar Affective Disorder Type 1 or Schizophrenia Body Mass Index outside the range of 18 to 33 inclusive Any significant current medical condition likely to interfere with conduct of the study or analysis of data Current use of psychoactive and / or medically significant medication as judged by a study medic, whether prescribed or bought over the counter (the contraceptive pill, the Depo-Provera injection or the progesterone implant will not result in exclusion) Ongoing psychopharmacological treatment for depression, including hypnotics (psychotherapy will be allowed as long as not newly-started in the last 6 weeks) High consumption of licit substances to an extent that would make complying with study protocol challenging (including alcohol, caffeine, nicotine) Past history of dependence to illicit substances, and any consumption of illicit substances in the three months prior to the study Currently pregnant or breast feeding Current, or a significant history of, gastro-intestinal disorder or irritable bowel syndrome Known lactase deficiency or any other problem absorbing lactose, galactose, or glucose Participation in a study that involves the use of a medication or novel vaccine within the last three months Participation in a study using the same tasks in the last two years Any physical (including visual and auditory) or language impairment that would make complying with the study protocol challenging
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Angharad de Cates, MRCPsych
Phone
+441865 618318
Email
angharad.decates@psych.ox.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Susannah Murphy, PhD
Phone
+441865 618313
Email
susannah.murphy@psych.ox.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Angharad de Cates, MRCPsych
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Psychiatry, Warneford Hospital, University of Oxford
City
Oxford
State/Province
Oxfordshire
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Angharad de Cates
Email
angharad.decates@psych.ox.ac.uk

12. IPD Sharing Statement

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Prucalopride and Cognition in Recovered Depression

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