DepressionPhase 1/2CONEARANCT02070783
Cognitive and Neural Effects of ARA290
A Phase 1/2 study testing ARA290 in people with Depression, run by Leiden University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Depression
- What is being tested?
- ARA290
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteNetherlands
- Study dates
- Feb 2012to Feb 2014
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Dutch-speaking
- Age 18-35
- Right-handedness
- BMI 18 to 33 kg/m2
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effects of ARA290 on the Cognitive and Neural Processing of Emotions in Healthy Volunteers
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.
Read the 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:
- 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.
- 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.
- Conditions
- Depression
- Being tested
- ARA290, Placebo
- Keywords
- depression, cognition, emotion perception, information processing
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARA290Drug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| ARA290 | Experimental | 11-amino acid, linear peptide ARA290; intravenous injection with 2 mg ARA290 (single dosage). Receives: Drug: ARA290 |
| Placebo | Placebo comparator | saline (NaCl 0.9%) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
performance on information processing test battery, particularly emotion recognition
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.
Measured: 1 week
Secondary outcomes (1)
• Performance on a task of working memory
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2014 (estimated)
- Study startFeb 2012
- Primary completionFeb 2013
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Willem Van der Does, Leiden University Medical Center
- Investigators
- Willem Van der Does, PhD, Principal investigator, Leiden University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02070783
- Sponsor's protocol ID
- 2010-024364-18
- Acronym
- CONEARA
- Status last verified
- Feb 2014
- First submitted
- 23 Feb 2014
- Last updated
- 25 Feb 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 19017170Miskowiak 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.
PubMed 21947319Cerit 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.
PubMed 26431906
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of ARA290 on the Cognitive and Neural Processing of Emotions in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02070783
- Acronym / sponsor ID
- CONEARA / 2010-024364-18
- Conditions
- Depression
- Keywords
- depression, cognition, emotion perception, information processing
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Study start
- Feb 2012
- Primary completion
- Feb 2013 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 25 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARA290 | Experimental | Drug: ARA29011-amino acid, linear peptide ARA290; intravenous injection with 2 mg ARA290 (single dosage). |
| Placebo | Placebo comparator | Drug: Placebosaline (NaCl 0.9%) |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Dutch-speaking
- Age 18-35
- Right-handedness
- BMI 18 to 33 kg/m2
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ARA290 | Drug | ARA290 |
| Placebo | Drug | Placebo |
Primary outcome
performance on information processing test battery, particularly emotion recognition
Time frame: 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.
1 secondary outcome
• Performance on a task of working memory
Time frame: 1 week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2014.
- Background: PubMed 19017170Brines 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.
- Background: PubMed 21947319Miskowiak 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.
- Derived from this study: PubMed 26431906Cerit 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Willem Van der Does, PhD principal investigator
Leiden University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ARA290 in people with Depression, run by Leiden University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
performance on information processing test battery, particularly emotion recognition (time frame: 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02070783, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2014.