Clinical trial NCT02070783: Cognitive and Neural Effects of ARA290
Official title: The Effects of ARA290 on the Cognitive and Neural Processing of Emotions in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Depression
Keywords: depression
cognition
emotion perception
information processing
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2014-02-25
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Studies on the hormone Erythropoietin (EPO) have indicated that EPO may have antidepressant properties. However, EPO may cause serious side-effects with repeated administration (thrombosis), which limits its usefulness as an antidepressant. ARA290 is a peptide that does not have the effects of EPO on blood cells but may still have its effect on brain function. In an attempt to replicate previous findings with (a single dose of) EPO in healthy volunteers, we study the effects of ARA290 on the cognitive and neural processing of emotions in healthy volunteers. We hypothesize that a single dose of ARA290 will lead to a positive shift in information processing compared to placebo, 7 days post-administration.

Detailed description: SUMMARY Rationale: Studies on the cognitive and neuronal effects of a single administration of Erythropoietin (EPO) in healthy volunteers and in depressed patients have suggested that EPO may have antidepressant effects. Due to its haematopoietic effects, EPO may cause serious side-effects with repeated administration, which limits its usefulness as an antidepressant. ARA290 is a peptide that does not have the haematopoietic effects of EPO but may still have its neurotrophic effects.

Objective: To study the effects of ARA290 on the cognitive and neural processing of emotions in healthy volunteers 7 days post-administration.

Study design: Randomized double-blind placebo-controlled experiment. Study population: Male and female healthy volunteers, n= 36; 18-35 yr old. Intervention: One group receives a single dose of 2 mg ARA290, the other group receives placebo.

Main study parameters/endpoints:

1. Behavioral study: Performance on an Emotional Test battery (ETB) which has been shown sensitive to antidepressant administration in healthy volunteers. The ETB includes a measure of facial expression recognition, emotional memory and attentional vigilance.
2. Neuroimaging study: Neural processing of emotions, in particular amygdala, hippocampal and VMPFC response to viewing facial stimuli expressing negative versus positive emotions.

Nature and extent of the burden and risks and benefits associated with participation:

Risks: No adverse events have been associated with the administration of a single dose of 70 -2000 μg ARA290 among 36 individuals, with the exception of one individual (with an undisclosed significant prior history of fainting) who fainted shortly after the intravenous dose administration of 700 μg ARA290 and recovered without medical intervention. Fourteen individuals have participated in a multiple dosing study with no serious adverse effects. Single doses of ARA290 in patients with renal impairment did not raise a safety signal.

Burden: Minimal. Emotional information processing test battery, burden comparable with playing computer games. fMRI measurement.

Benefits: Probably none. Possibly transient and small improvement of mood state. Financial compensation for participating.

Eligibility criteria: Inclusion Criteria:

* Dutch-speaking
* Age 18-35
* Right-handedness
* BMI 18 to 33 kg/m2

Exclusion Criteria:

* Major physical illness, such as diabetes, thyroid disease, epilepsy, stroke, multiple sclerosis, pituitary disease, or any other serious medical condition.
* Any current or past psychiatric disorder, including subclinical claustrophobia if severe enough to cause anxiety during scanning.
* Using medication likely to interfere with the study, including OTC (over the counter) medication (e.g., St John's Wort) and benzodiazepines.
* Pregnancy or breastfeeding
* Use of any nicotine products or soft drugs (hash, marihuana) in the three months prior to the study
* Any hard drug use (including XTC) (lifetime)
* Alcohol use of more than 14 units per week or more than 4 units on any day during the week prior to the study or during the study period.

Primary outcomes:
measure: performance on information processing test battery, particularly emotion recognition
timeFrame: 1 week
Secondary outcomes:
measure: • Performance on a task of working memory
timeFrame: 1 week
Other outcomes:
measure: Neural response to angry faces
timeFrame: 1 week
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
Study officials:
affiliation: Leiden University
name: Willem Van der Does, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brines M, Cerami A. Erythropoietin-mediated tissue protection: reducing collateral damage from the primary injury response. J Intern Med. 2008 Nov;264(5):405-32. doi: 10.1111/j.1365-2796.2008.02024.x.
citation: Miskowiak KW, Vinberg M, Harmer CJ, Ehrenreich H, Kessing LV. Erythropoietin: a candidate treatment for mood symptoms and memory dysfunction in depression. Psychopharmacology (Berl). 2012 Feb;219(3):687-98. doi: 10.1007/s00213-011-2511-1. Epub 2011 Sep 23.
citation: Cerit H, Veer IM, Dahan A, Niesters M, Harmer CJ, Miskowiak KW, Rombouts SA, Van der Does W. Testing the antidepressant properties of the peptide ARA290 in a human neuropsychological model of drug action. Eur Neuropsychopharmacol. 2015 Dec;25(12):2289-99. doi: 10.1016/j.euroneuro.2015.09.005. Epub 2015 Sep 18.