Studying the impact of Doxycycline on fear memory in healthy individuals
| ISRCTN | ISRCTN66987216 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN66987216 |
| Secondary identifying numbers | DoxMem |
- Submission date
- 05/06/2015
- Registration date
- 23/06/2015
- Last edited
- 10/07/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English summary of protocol
Background and study aims
Anxiety disorders and phobias are thought to result from pathological learning. The erasing of fear memory could therefore have a therapeutic effect. Memory is transformed from an unstable into a stable form during consolidation (the strengthening of memory) in a process that depends on protein synthesis (i.e. the production of protein). Re-activation of an existing memory can make that memory unstable, in particular if new information is being added to the old memory that is being recalled. This suggests that memory can be erased by first re-activating an old memory, and then blocking the synthesis of proteins necessary for the strengthening of that memory by giving a drug (i.e. stopping the proteins that are needed to strengthen the memory). The antibiotic Doxycyclin blocks the activity and the synthesis of specific proteins, and has been shown to weaken memory of general knowledge. Here, we are testing the effect of Doxycyline on the strengthening of human fear memory (phase 1). If phase 1 is successful, then in phase 2 we will test its effect on re-activation of old fear memories. Phase 1 will prove the potential of the drug to weaken fear memory, and phase 2 its potential as a therapy for erasing already strengthened fear memory. Phase 2 will only take place if phase 1 is successful. We will study the impact of Doxycyclin by giving Doxycyclin, or placebo, to healthy individuals and testing their memory.
Who can participate?
Healthy adults between 18-40 years of age.
What does the study involve?
The study is conducted in two separate phases. For both phases, participants are physically examined, and give blood and urine samples. Participants who pass the medical examination are invited for study visit 2. Participants from phase one fill in four questionnaires and randomly (by chance) receive a single dose of either Doxycycline (an antibiotic) or placebo (dummy). Participants from phase two skip this step and instead do it during study visit 3. Next, electrodes for measuring ECG (heart activity), EMG (muscle activity), skin conductance, and also breathing, are placed on the participants from both phases. Participants then perform a computer task during which they will learn the association between a neutral stimulus (a geometric shape on a screen) and a fearful stimulus (mild electric stimulation) and as a result, will form a fear memory. For the second phase study, participants additionally come in for study visit 3. The same procedures as for study visit 2 is repeated, and the fear memory that was learned during the previous study visit is re-activated. Participants from both study phases attend study visit 4. The same procedures as for study visit 2, with the exception of drug administration, is repeated. The previously formed fear memory is then recalled.
What are the possible benefits and risks of participating?
Doxycycline is an approved drug with rare serious side effects. It may cause abdominal or stomach tenderness, in severe cases allergic reactions. Participants have no direct benefit from taking the study medication. This study will potentially benefit patients with anxiety disorders.
Where is the study run from?
The study will be conducted at the Psychiatric University Hospital Zürich (PUK ZH)
When is study starting and how long is it expected to run for?
July 2015 to July 2018
Who is funding the study?
The University of Zürich (UZH)
Who is the main contact?
Professor Dominik R. Bach
dominik.bach@uzh.ch
Contact information
Scientific
Comparative Emotion Group
Prof. Dr. Dominik R Bach
Psychiatric Hospital, University of Zurich
Lenggstrasse 31
Zurich
8032
Switzerland
 ORCID ID |
0000-0003-3717-2036 |
|---|
Study information
| Study design | Randomised placebo-controlled double-blind trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | A randomised, double-blind, placebo-controlled, two-phase study on the impact of Doxycycline on fear memory in healthy individuals |
| Study objectives | Null hypothesis: Doxycyclin and placebo groups do not differ in fear recall |
| Ethics approval(s) | Kantonale Ethikkommission Zürich, 23/04/2015, ref: KEK-ZH-Nr.2014-0669 |
| Health condition(s) or problem(s) studied | Fear memory |
| Intervention | A single dose 200 mg of Doxycycline or placebo |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Doxycycline |
| Primary outcome measure | Current primary outcome measures as of 25/08/2016: The difference in fear memory recall between a fear-conditioned CS+ and a safety-conditioned CS-, as estimated from startle eye blink EMG (The initially registered primary outcome, skin conductance responses, is not measured during the memory recall phase, due to a change in study design before inclusion of the first participant) Previous primary outcome measures: The difference in fear memory between a fear-conditioned CS+ and a safety-conditioned CS-, as estimated from skin conductance responses. |
| Secondary outcome measures | Current secondary outcome measures as of 25/08/2016: Fear memory indices derived from skin conductance responses and heart rate during fear acquisition and re-learning Previous secondary outcome measures: A fear memory index derived from heart rate, pupil size, and startle response quantified via EMG of the M. orbicularis oculi |
| Overall study start date | 27/03/2015 |
| Completion date | 27/07/2018 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 160 |
| Total final enrolment | 160 |
| Key inclusion criteria | 1. Informed consent as documented by signature 2. Age 18 – 40 years |
| Key exclusion criteria | 1. Allergy to Doxycycline or to any other ingredient in the named drug 2. Use of any drugs in the 2 weeks prior to the study with the exception of contraceptive drugs and incidental use of NSARs or paracetamol 3. Women who are pregnant or breast feeding 4. Intention to become pregnant during the course of the study 5. Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, combined with a mechanical contraceptive (condom, diaphragm) 6. Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.) 7. Any history of psychiatric, neurological, dependence or systemic/rheumatic disease 8. Known or suspected non-compliance, drug or alcohol abuse 9. Inability to follow the procedures of the study, e.g. due to language problems 10. Participation in another study with investigational drug within the 30 days preceding and during the present study 11. Previous enrolment into the current study 12. Members of the study team and their family members and dependants |
| Date of first enrolment | 01/11/2015 |
| Date of final enrolment | 27/03/2018 |
Locations
Countries of recruitment
- Switzerland
Study participating centre
Lenggstrasse 31
Postfach 1931
Zürich
8032
Switzerland
Sponsor information
University/education
c/o Prof. Dominik R. Bach
Psychiatric University Hospital (Psychiatrische Universitätsklinik)
Lenggstrasse 31
Postfach 1931
Zürich
8032
Switzerland
| Website | http://www.pukzh.ch/ |
|---|---|
"ROR" |
https://ror.org/01462r250 |
Funders
Funder type
University/education
Government organisation / Universities (academic only)
- Alternative name(s)
- University of Zurich, Switzerland, University of Zurich, UZH
- Location
- Switzerland
Results and Publications
| Intention to publish date | 27/07/2020 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Stored in repository |
| Publication and dissemination plan | The trialists intend to publish the results of the study in a peer-reviewed journal within 2 years following data collection. Anonymity of participants shall be guaranteed. |
| IPD sharing plan | After final publication of the results, anonymised participant-level data will be made publicly available on zenodo.org, following the procedures mandated by Swiss Human Research Law. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/07/2018 | 09/07/2019 | Yes | No |
| Dataset | 18/09/2019 | 10/07/2023 | No | No | |
| Results article | 15/10/2019 | 10/07/2023 | Yes | No |
Editorial Notes
10/07/2023: Publication reference and dataset added.
09/07/2019: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
25/06/2018: IPD sharing statement added.
16/04/2018: The following changes were made to the trial record:
1. The recruitment end date was changed from 27/07/2017 to 27/03/2018.
2. The target number of participants was changed from 120 to 160.
25/08/2016: The recruitment start date was changed from 27/07/2015 to 01/11/2015.
