Neural Response to Catecholamine Depletion in Subjects Suffering From Bulimia Nervosa in Their Past and Healthy Controls

NCT02179814 | Suspended

• 3 other identifiers: 132/102011DR101132003B_138264 / 1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Bulimia nervosa is a severe psychiatric disorder characterized by recurrent binge eating episodes followed by inappropriate compensatory behavior to prevent weight gain such as self-induced vomiting. With this project, the investigators want to investigate the role of the neurotransmitter dopamine in bulimia nervosa. Dopamine is reported to have an important influence on the neural reward system and is involved in the processing of gains and losses. The reward system is functionally connected to the individual perception of rewards in the environment. A previous study revealed that under catecholamine depletion including dopamine depletion women suffering from bulimia nervosa in their past reported mild bulimic symptoms and their reward processing became dysfunctional: their ability to use rewarding stimuli for task solving was diminished. The aim of this study is to investigate the role of reduced dopamine availability in the development or maintaining of bulimia nervosa and in the dysfunctional processing of rewarding stimuli and negative visual information. Therefore, the investigators hypothesize that catecholamine depletion achieved by oral administration of alpha-methyl-paratyrosine (AMPT) will induce mild bulimic symptoms in females suffering from bulimia nervosa in their past. In addition, they will reveal dysfunctions in reward and emotional processing under catecholamine depletion. Using functional magnetic resonance imaging, the investigators propose that a reduced activation of the nucleus accumbens, a neural structure of the reward system, will be the neural correlate of this dysfunctional reward processing. Furthermore, the amygdala, a neural structure that is involved in emotional processing, will show a higher activation under catecholamine depletion. Genetic factors additionally have an influence on the dopaminergic system. Therefore, the investigators hypothesize that genetic factors, for example the COMT val-158-met polymorphism may have an effect on the behavioral and neural response to catecholamine depletion. In sum, this investigation may help to understand which changes in reward and emotional processing may lead to a reoccurrence of bulimic symptoms. In future, the findings of this study may help to develop individual pharmacological and psychotherapeutical interventions to enhance the outcome of treatment.

Conditions

Bulimia Nervosa; Eating Disorders; Dopamine; Reward; Catechol-O-methyltransferase

Keywords

bulimia nervosa; dopamine; reward; catechol-O-methyltransferase; gene; catecholamines; alpha-methyl-para-tyrosine; magnetic resonance imaging

Outcome Measures

Primary Outcomes (1)

• Number of participants with side effects

  1 year

Secondary Outcomes (3)

• Performance differences in behavioral tasks after catecholamine depletion

  4 years

• Differences in neural activation assessed during functional magnetic resonance imaging (fMRI) in the different conditions

  4 years

• Differences in neural activation assessed during functional magnetic resonance imaging (fMRI) and in performance in behavioral tasks in the different conditions between the different genotypes

  4 years

Study Arms (2)

AMPT

EXPERIMENTAL

Experimental: alpha-methyl-paratyrosine (AMPT, trade name: Demser), body-weight adjusted dosage (40 mg/kg body weight, maximum 4000mg) at 4 time points over 24 hours

Drug: AMPT/ Demser

Diphenhydramine & placebo

SHAM COMPARATOR

Diphenhydramine (25mg, trade name in Switzerland: Benocten) at the first medication intake time point, placebo at the second to fourth intake time point (medication intake over 24 hours)

Drug: Diphenhydramine; Drug: Placebo

Interventions

AMPT/ Demser DRUG

alpha-methyl-paratyrosine (AMPT, trade name: Demser) body-weight adjusted dosage (40 mg/kg body weight, maximum 4000mg) at 4 medication intake time points over 24 hours

AMPT

Diphenhydramine DRUG

Diphenhydramine (25mg) at the first medication intake time point

Also known as: Benocten (trade name in Switzerland)

Diphenhydramine & placebo

Placebo DRUG

Placebo at the second, third and fourth medication intake time point

Diphenhydramine & placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• female
• age: 18-60
• caucasian ethnicity
• right handedness
• normal or corrected to normal vision and hearing performance
• remitted bulimic participants: have met the DSM IV criteria for bulimia nervosa in the past
• remitted bulimic participants: have been asymptomatic for at least1 month
• signed written informed consent

You may not qualify if:

• healthy volunteers: any lifetime psychiatric diagnosis
• healthy volunteers: any lifetime psychiatric diagnosis in first-degree relatives
• no or impaired understanding of the tasks or the risks of the study
• medical or neurological illnesses likely to affect physiology or anatomy
• suicidal ideation or suicide attempts within the last 8 weeks
• current use of psychotropic drugs
• history of drug including alcohol and nicotine (not more than 10 cigarettes per day) abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM IV criteria) longer than 2 years
• asthma
• glaucoma
• pyloroduodenal obstruction (gastrointestinal stenosis)
• current pregnancy
• current breast feeding
• cardiac pacemaker
• heart or brain surgery
• metallic implants and alien objects in the body

Sponsors & Collaborators

• University of Bern: lead
• Insel Gruppe AG, University Hospital Bern: collaborator
• University of Zurich: collaborator

Study Sites (1)

University Hospital of Psychiatry, University of Bern

Bern, 3000, Switzerland

Location

Related Publications (3)

• Hasler G, Fromm S, Carlson PJ, Luckenbaugh DA, Waldeck T, Geraci M, Roiser JP, Neumeister A, Meyers N, Charney DS, Drevets WC. Neural response to catecholamine depletion in unmedicated subjects with major depressive disorder in remission and healthy subjects. Arch Gen Psychiatry. 2008 May;65(5):521-31. doi: 10.1001/archpsyc.65.5.521.

  PMID: 18458204 BACKGROUND

• Grob S, Stern J, Gamper L, Moergeli H, Milos G, Schnyder U, Hasler G. Behavioral responses to catecholamine depletion in unmedicated, remitted subjects with bulimia nervosa and healthy subjects. Biol Psychiatry. 2015 Apr 1;77(7):661-7. doi: 10.1016/j.biopsych.2013.09.013. Epub 2013 Oct 25.

  PMID: 24209774 BACKGROUND

• Homan P, Grob S, Milos G, Schnyder U, Hasler G. Reduction in total plasma ghrelin levels following catecholamine depletion: relation to bulimic and depressive symptoms. Psychoneuroendocrinology. 2013 Sep;38(9):1545-52. doi: 10.1016/j.psyneuen.2012.12.024. Epub 2013 Jan 16.

  PMID: 23333252 BACKGROUND

MeSH Terms

Conditions

Bulimia Nervosa; Feeding and Eating Disorders

Interventions

alpha-Methyltyrosine; Diphenhydramine

Condition Hierarchy (Ancestors)

Mental Disorders; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Methyltyrosines; Tyrosine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Gregor Hasler, Prof. Dr. med

  University Hospital of Psychiatry, University of Bern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2014
• First Posted: July 2, 2014
• Study Start: February 20, 2012
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2022
• Last Updated: January 24, 2019

Record last verified: 2019-01

Locations

CH (1)