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CompletedNCT03450239Updated Apr 5, 2018

Functional Magnetic Resonance Imaging (fMRI) Investigation Into Compulsivity in Anorexia

An interventional study of MRI in Anorexia Nervosa in Remission (Disorder) and Compulsive Behavior, sponsored by University of Oxford. Completed at 1 site in United Kingdom. Open to female participants aged 18 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-04-05.

Sponsored by University of Oxford · Not applicable, Interventional, and Basic science

Phase
Not applicable
Study type
Interventional
Enrollment
40
Allocation
Non-randomized
Ages
18 Years to 40 Years
Sex
Female
01

Study summary

The investigators will examine compulsivity in those who have recovered from anorexia nervosa, using a multi-modal MRI study. The neural activation of key fronto-striatal areas will be explored using a task which examines set-shifting and reversal-learning, two key components of compulsivity. Additionally, the functional networks displayed during resting-state MRI will be examined between groups, as will the neurochemicals present (using Magnetic Resonance spectroscopy).

Read the detailed description

The investigators will perform four different MRI (Magnetic Resonance Imaging) scans during one scanning session on those who have recovered from anorexia nervosa (AN) and healthy controls.

Participants will come to the Warneford hospital for a 2.5 hour screening visit, which will consist of questionnaires and interviews to determine their medical and psychiatric history and current mood, along with a practice of the task they'll do in the scanner. Participants will also complete two tasks which measure compulsivity and can be correlated with their brain activity in the scans. The investigators will also go through a scanning safety form with participants at this time.

Participants will also attend a scanning visit, which will last 1.5 hours. One of the scans will look at how the brain responds to a particular task. This task will examine aspects of compulsivity (which is rigidly repeating actions that aren't rewarding) by using face and house stimuli (see reference 1).

The investigators will also perform a scan when participants are at rest, in order to see if there are differences in the way areas of the brain connect to each other who used to have AN. The scientific literature indicates that there may be differences in the some key brain networks, including one which is thought to be involved in reflection and the self (the default mode network), which might also be linked to compulsivity (see reference 2).

This study will also further investigate some initial pilot findings using Magnetic Resonance Spectroscopy, which allows researchers to examine the levels of different neurochemicals in the brain. It has been found that those with a current diagnosis of AN have lower levels of glutamate (a key brain chemical) compared to healthy controls, which is a finding we seek to extend in those who have recovered from AN (see reference 3).

Aims: The investigators aim to see whether there are differences in the brains of those who have recovered from anorexia compared to those who have never had an anorexia diagnosis. This will be both at rest, and whilst participants are doing a task which measures compulsivity, as compulsivity is thought to be a particular risk factor for eating disorders.

Value: If the investigators are able to identify differences, these might reflect underlying risk factors for eating disorders, which could lead to potential future treatments or prevention schemes.

02

Conditions studied

  • Anorexia Nervosa in Remission (Disorder)
  • Compulsive Behavior

Keywords

  • MRI
03

Who can participate

Ages eligible
18 Years to 40 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

Inclusion criteria

  • Able and willing to give informed consent
  • BMI over 18.5 and has remained so for the last year
  • Score lower than mean+1 standard deviation of global mean scores for young women on the EDE
  • Fluent English speaker
  • Former diagnosis of anorexia nervosa in relevant group

Exclusion criteria

Exclusion Criteria:

  • Any current diagnosis of a psychiatric disorder which in the investigator's opinion could impact study results (e.g. significant depression, anxiety or OCD).
  • Any current psychotropic medications.
  • Eyesight problems that would prohibit participating in a task-fMRI study.
  • Current regular cigarette smoking of over 5 cigarettes per day.
  • Recent use of illicit drugs.
  • Alcohol intake which indicates an element of alcohol abuse; or unwillingness to refrain from drinking the night before the study visit.
  • Any contraindications to MRI scanning (including claustrophobia).
  • Participant is pregnant or breast-feeding.
04

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
40 participants (actual)

Study arms

  • Experimental
    Recovered from anorexia nervosa

    Women who have recovered from Anorexia Nervosa for over a year. BMI over 18.5, aged 18-40, scores on Eating Disorder Examination (EDE) within 1 standard deviation of the global mean. All these participants undergo an MRI scan.

    Other: MRI

  • Experimental
    Healthy controls

    Healthy control women. BMI over 18.5, aged 18-40, scores on EDE within 1 standard deviation of the global mean. All these participants undergo an MRI scan.

    Other: MRI

Interventions

  • OtherMRI

    MRI scan, including structural imaging, functional imaging (both task-related and structural), and Magnetic Resonance Spectroscopy.

05

What researchers measure

Primary outcomes

  1. Blood Oxygen-Level Dependent (BOLD) signal whilst performing set-shifting and reversal-learning

    BOLD signal differences between groups during the set-shifting and reversal-learning elements of a task: will be examined in orbitofrontal cortex, dorsolateral prefrontal cortex, and striatum. Analyse using a repeated measures ANOVA with region as within-subject factor and group as between-subject factor. Follow up significant interactions with paired t-tests.

    Time frame: 1 day (During MRI scan)

Secondary outcomes

  1. Differences between groups in the connectivity of the fronto-parietal and default mode networks using independent components analysis, dual regression and permutation testing across the brain.

    A resting state scan will be performed, and an Independent Components Analysis will be performed to identify networks. Dual regression using fronto-parietal and default mode network to test whether there are group differences. This procedure regresses the group-spatial-maps into each subject's 4D dataset to give a set of timecourses, then regresses these timecourses into the same 4D dataset to get a subject-specific set of spatial maps. Then, the researchers will compare the spatial maps across groups of subjects to look for group differences in connectivity across the brain, using randomise permutation testing.

    Time frame: 1 day (During MRI scan)

  2. The correlation of the default mode network and frontoparietal network activity with perseverative errors on the Wisconsin Card Sorting Task across groups

    Correlate perseverative errors on Wisconsin Card Sorting Task with connectivity level of Default Mode Network (DMN) and frontoparietal network

    Time frame: 1 day (During MRI scan)

  3. Investigate a difference in levels of glutamate between groups

    Concentration of cortical glutamate in those who have recovered from anorexia relative to controls. Will be analysed using LCModel to quantify metabolites, then an independent samples t-test.

    Time frame: 1 day (During MRI scan)

  4. Examine differences between groups on an impulsivity measure

    Differences between scores on the Affective Go/No-Go Task. Analysed using a independent-samples t-test.

    Time frame: 1 day (During MRI scan)

06

Study locations

1 site
  • Department of Psychiatry, University of Oxford
    Oxford, Oxfordshire OX3 7JX, United Kingdom
07

References and documents

Publications

  • Chamberlain SR, Menzies L, Hampshire A, Suckling J, Fineberg NA, del Campo N, Aitken M, Craig K, Owen AM, Bullmore ET, Robbins TW, Sahakian BJ. Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives. Science. 2008 Jul 18;321(5887):421-2. doi: 10.1126/science.1154433. PubMed 18635808 ↗
  • Boehm I, Geisler D, King JA, Ritschel F, Seidel M, Deza Araujo Y, Petermann J, Lohmeier H, Weiss J, Walter M, Roessner V, Ehrlich S. Increased resting state functional connectivity in the fronto-parietal and default mode network in anorexia nervosa. Front Behav Neurosci. 2014 Oct 2;8:346. doi: 10.3389/fnbeh.2014.00346. eCollection 2014. PubMed 25324749 ↗
  • Godlewska BR, Pike A, Sharpley AL, Ayton A, Park RJ, Cowen PJ, Emir UE. Brain glutamate in anorexia nervosa: a magnetic resonance spectroscopy case control study at 7 Tesla. Psychopharmacology (Berl). 2017 Feb;234(3):421-426. doi: 10.1007/s00213-016-4477-5. Epub 2016 Dec 1. PubMed 27909746 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT03450239
Lead sponsor
University of Oxford
Responsible party
Sponsor
First posted
Mar 1, 2018
Start date
May 5, 2017
Primary completion
Feb 7, 2018
Completion
Feb 7, 2018
Last update
Apr 5, 2018

Study contacts

Philip J Cowen, Prof
principal investigator · University of Oxford

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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