Cognitive and Neural Effects of ARA290

Phase 1

Completed

• Conditions: Depression
• Interventions: Drug: ARA290; Drug: Placebo

• Registration Number: NCT02070783
• Lead Sponsor: Leiden University Medical Center

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.

Study Timeline

• Study Start: 2012-02
• Primary Completion: 2013-02
• Status Verified: 2014-02
• Study Completion: 2014-02
• Study First Submitted: 2014-02-23
• Study First Submitted QC: 2014-02-23
• Last Update Submitted: 2014-02-23
• Study First Posted: 2014-02-25
• Last Update Posted: 2014-02-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ARA290	ARA290	11-amino acid, linear peptide ARA290; intravenous injection with 2 mg ARA290 (single dosage).
Placebo	Placebo	saline (NaCl 0.9%)

Primary Outcome Measures

Name	Time	Method
performance on information processing test battery, particularly emotion recognition	1 week	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.

Secondary Outcome Measures

Name	Time	Method
• Performance on a task of working memory	1 week

Trial Locations

Locations (1)

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands