The impact of the circadian clock on retinal function
| ISRCTN | ISRCTN67032901 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN67032901 |
- Submission date
- 23/03/2024
- Registration date
- 28/03/2024
- Last edited
- 28/03/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Eye Diseases
Plain English Summary
Background and study aims
Previous research indicates that visual functions vary throughout the day, likely due to natural body rhythms. However, it is unclear whether these changes are driven by the body's internal clock (circadian rhythm) or other factors. To understand this better, this study aims to separate the effects of circadian rhythms and other processes on retinal function. The research will focus on how the eye responds to light and perceives images. By studying these responses, the researchers hope to gain insights into how light affects the internal body clock and vice versa, potentially leading to refinements in our understanding of circadian rhythms.
Who can participate?
Adult healthy volunteers aged from 18 to 35 years old
What does the study involve?
Participants will spend 40 hours in a controlled environment, with alternating periods of wakefulness and sleep in dim or no light. During wakeful periods, they will undergo tests to assess their ability to see patterns and how their pupils react to light. Retinal sensitivity is expected to change depending on the time of day.
What are the possible benefits and risks of participating?
Participants in this study will play a crucial role in the advancement of scientific knowledge, with no immediate personal advantage or benefit. The study design ensures no long-term negative impacts on physical health or mental well-being. All necessary precautions will be taken to ensure participant comfort and engagement throughout the study, including measures to address any discomfort or difficulties experienced during the various procedures. The main experiment in this study consists of a 40-hour sleep-wake protocol, involving strict adherence to a predetermined sleep-wake schedule. Although participants may find it difficult to adjust to this schedule, the risks associated with the protocol are considered minimal. Temporary disruptions to circadian rhythms may occur as a consequence, leading to changes in sleep quality, mood, and overall well-being, similar to experiencing “jet lag” when traveling across time zones. However, participants will be closely monitored, and steps will be taken to ensure their comfort and well-being throughout the study. During certain psychophysical and pupillometric measurements, participants may experience strain and discomfort. To minimize these effects, participants will have an opportunity to familiarize themselves with the visual tasks and tests before committing to the experiment. Throughout the study, the study team will closely monitor participant well-being and intervene if any participants report feeling uncomfortable. Before entering the main study, participants will provide blood samples. The process of drawing blood, while generally safe, carries some potential risks including discomfort, bruising at the puncture site and in rare cases, the possibility of permanent nerve damage. Additionally, there is a small chance of infection or allergic reactions to disinfectants, adhesive materials, or bandages used during the procedure. These risks will be managed through properly trained personnel, adherence to sterile techniques, and prompt attention to any adverse reactions. Participants in this study are required to adhere to a regular sleep-wake cycle for the whole study period of 3 weeks, which some individuals may find challenging. Through our screening methods, the study team will identify individuals who are likely to have no difficulties in maintaining a regular sleep-wake cycle. Additionally, participants will be required to abstain from caffeine and alcohol during the study, which may pose some difficulty for some individuals. During the screening process, the study team will select participants who have low to moderate consumption and are comfortable abstaining from these substances for the duration of the study. They are also asked to wear an actigraph tracker, which is no larger than a wristwatch, during this time. While some participants may find wearing the device intrusive or challenging, it provides valuable data for the research. In summary, the challenges and discomfort associated with this study are considered minor, as they are outweighed by the potential for significant advancements in fundamental biological and biomedical knowledge. The insights gained from this research will contribute to a better understanding of the interaction of visual processing of light and circadian signals. The study team will be committed to prioritizing participant well-being, maintaining their comfort, and ensuring their understanding and informed consent throughout the research process.
Where is the study run from?
Max Planck Institute for Biological Cybernetics
When is the study starting and how long is it expected to run for?
June 2023 to May 2025
Who is funding the study?
Max Planck Society for the Advancement of Science
Who is the main contact?
Prof Manuel Spitschan, manuel.spitschan@tuebingen.mpg.de
Contact information
Public, Scientific, Principal Investigator
Max-Planck-Ring 8-14
Tübingen
72076
Germany
 ORCID ID |
0000-0002-8572-9268 |
|---|---|
| Phone | +49 (0)7071 601 1670 |
| manuel.spitschan@tuebingen.mpg.de |
Public, Scientific, Principal Investigator
Max-Planck-Ring 8-14
Tübingen
72076
Germany
| ORCID ID |
0000-0001-5047-5205 |
|---|---|
| Phone | +49 (0)7071 601 215 |
| hannah.heinrichs@tuebingen.mpg.de |
Study information
| Study design | Single-blinded interventional trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Laboratory |
| Study type | Other |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | Within-subjects ultra-short sleep-wake protocol for characterising circadian variations in retinal function |
| Study hypothesis | The circadian clock affects retinal function and sensitivity |
| Ethics approval(s) |
Approved 27/10/2023, Medical Ethics Committee of the Technical University of Munich (Ismaninger Straße 22, Munich, 81675, Germany; +49 (0)89 4140 7737; ethikkommission@mri.tum.de), ref: 2023-369-S-SB |
| Condition | Circadian modulation of retinal function |
| Intervention | Ultra-short sleep-wake cycle intervention: All participants undergo the same protocol and there are no study arms. The intervention is geared to decouple circadian from homeostatic parameters. Participants will stay in a controlled time-isolating environment under dim light conditions and adhere to an ultra-short sleep-wake cycle, alternating between 2h30m of wake time in dim light and 1h15m hour of sleep in no light. |
| Intervention type | Behavioural |
| Primary outcome measure | 1. Pupil responses to silent-substitution modulations (L-M, S, L+M+S, Mel) are measured once using a Maxwellian multi-primary pupillometer during each ultra-short sleep-wake cycle 2. Psychophysical thresholds to silent-substitution modulations (L-M, S, L+M+S) are measured once using the Metropsis stimulus system during each ultra-short sleep-wake cycle |
| Secondary outcome measures | 1. Core body temperature is measured using telemetry pills continuously during the entire experiment. 2. Distal-proximal temperature measured using skin temperature sensors continuously during the entire experiment. 3. Rest-activity cycles are measured using actigraphs continuously during the entire experiment. 4. ECG is measured using a heart rate monitor continuously during the entire experiment. 5. Glucose concentrations are measured using a CGM continuously during the entire experiment. 6. Ocular structures are measured using OCT once per ultra-short sleep-wake cycle 7. Salivary cortisol concentrations are measured using Salivette and later ELISAs every 45 minutes during each ultra-short sleep-wake cycle 8. Salivary melatonin concentrations are measured using Salivette and later ELISAs every 45 minutes during each ultra-short sleep-wake cycle 9. Intraocular pressure is measured using a tonometer once per ultra-short sleep-wake cycle 10. Psychomotor vigilance is measured using the Psychomotor Vigilance Test (PVT) once per ultra-short sleep-wake cycle 11. Blood pressure is measured using a wearable blood pressure monitor every 45 minutes per ultra-short sleep-wake cycle |
| Overall study start date | 01/06/2023 |
| Overall study end date | 31/05/2025 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 35 Years |
| Sex | Both |
| Target number of participants | 12 |
| Participant inclusion criteria | 1. Good physical health 2. Good mental health 3. Good ocular health 4. Normal or corrected-to-normal vision 5. Normal colour vision |
| Participant exclusion criteria | 1. Too low (<18.5) or too high (>25) BMI 2. Alcohol abuse (AUDIT >7) 3. Self-report of depressive symptoms 4. Self-report of history of anxiety disorder 5. Extreme chronotype 6. Any use of medications (except for hormonal contraception) 7. Smoking 8. Photosensitive epilepsy 9. Shift work 10 . Transmeridian travel 11. Pregnancy 12. Endocrine alterations 13. Drug use during the study 14. Alcohol use during the study |
| Recruitment start date | 01/01/2024 |
| Recruitment end date | 30/09/2024 |
Locations
Countries of recruitment
- Germany
Study participating centre
Tübingen
72072
Germany
Sponsor information
Research organisation
Max-Planck-Ring 8-14
Tübingen
72076
Germany
| Phone | +49 (0)7071 601 1670 |
|---|---|
| agms@tuebingen.mpg.de | |
| Website | https://www.kyb.tuebingen.mpg.de/en |
"ROR" |
https://ror.org/026nmvv73 |
Funders
Funder type
Research organisation
Government organisation / Research institutes and centers
- Alternative name(s)
- Max Planck Society for the Advancement of Science, Max-Planck-Gesellschaft zur Förderung der Wissenschaften, Max Planck Society, MPG
- Location
- Germany
Results and Publications
| Intention to publish date | 01/06/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in publicly available repository, Published as a supplement to the results publication |
| Publication and dissemination plan | We are dedicated to ensuring the robustness and transparency of the findings of this research, and its dissemination. First, we will present our results at relevant academic conferences, fostering discussion and feedback to ensure adequate data processing. All resources, including code, data, recruitment materials will be made openly available on FigShare and GitHub in order to promote transparency and reproducibility. Finally, where applicable, we are committed to engage with the public to convey the importance and applicability of the presented research, as well as to foster a better understanding of the underlying biological phenomena, such as circadian rhythms, sleep-wake behaviour and visual performance. |
| IPD sharing plan | The datasets generated and analysed during the study will be published as a supplement to the results publications. All data will be available on our GitHub (https://github.com/tscnlab) repository and/or FigShare under an open-access license. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol (preprint) | 02/03/2024 | 28/03/2024 | No | No |
Editorial Notes
26/03/2024: Study's existence confirmed by the Ethics Committee of the Technical University of Munich.
