Glaucoma, Open-Angle Glaucoma, Primary Open Angle Glaucoma (POAG)
Conditions
Keywords
Glaucoma, Semaglutide, Rybelsus, Primary Open Angle Glaucoma, GLP-1RA, Photopic Negative Response, GLP-1
Brief summary
The aim of this clinical trial is to investigate whether oral semaglutide can be used to treat open-angle glaucoma. The main question it aims to answer is: Does oral semaglutide safely improve inner retinal function in patients with open-angle glaucoma as measured by the photopic negative response of the electroretinogram. Researchers will compare oral semaglutide to a placebo (a look-alike substance that contains no drug). Participants will: * Take semaglutide or a placebo every day for 6 months. * Visit the clinic 5 times in total for tests and interviews: At baseline (the first day they are included in the study), after 1 month, after 2 months, after 3 months, and after 6 months (the last day they are included in the study).
Interventions
DRUGOral semaglutide
Participants will receive oral semaglutide once daily. 1. Starting dose 3 mg/day for one month (day 1-28) 2. Intermediate dose 7 mg/day for one month (day 29-56) 3. Maintenance dose 14 mg/day (day 57-182)
DRUGPlacebo
Participants will receive an oral placebo once daily. 1. Placebo tablets received on visit 1 (baseline) for one month (day 1-28) 2. Placebo tablets received on visit 2 (month 1) for one month (day 29-56) 3. Placebo tablets received on visit 3 (month 2) for four months (day 57-182)
Sponsors
Glostrup University Hospital, Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to read and speak Danish * 45 years or older at the time of inclusion * Visual acuity equal to or above 0.5 in the study eye * Diagnosis of POAG with MD ≤ 16 dB with repeatable and reliable (false positive less than 15 %) VF loss measured by standard automated perimetry on at least one eye * Receiving IOP-lowering glaucoma treatment * Nerve fiber layer defects identified by OCT
Exclusion criteria
* Diabetes or renal impairment * Medical history of significant eye disease (including ocular trauma) other than glaucoma * Ocular inflammation/infection within three months from inclusion * Intraocular surgery 3 months before inclusion * Smoker at the time of inclusion * Pregnant or breast-feeding * Females of childbearing potential who are not using adequate contraceptive, which includes the following: Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal, progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable; Intrauterine device (IUD); Intrauterine hormone-releasing system (IUS); Bilateral tubal occlusion; Vasectomised partner; Sexual abstinence * Subjects allergic to drug ingredients administered during the trial * Subjects with untreated severe systemic disease or malignancies * Previous history of pancreatitis * BMI \< 18.5 * Subjects receiving treatment with: Dipeptidyl peptidase-4 inhibitors; Other GLP-1RAs; Insulin; Insulin analogues; Sulfonylurea; Systemic corticosteroids; Immunosuppressants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Photopic negative response of the electroretinogram after 6 months | From baseline to month 6. | Change in the inner retinal function assessed by mean change in the photopic negative response of the electroretinogram. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Photopic negative response of the electroretinogram after 3 months | From baseline to month 3. | Change in the inner retinal function assessed by mean change in the photopic negative response of the electroretinogram. |
| Pelli-Robson chart contrast sensitivity test | From baseline to month 6. | Functional glaucoma progression assessed using the Pelli-Robson chart contrast sensitivity test. |
| Health-related quality of life (HRQoL) | From baseline to month 6. | Health-related quality of life (HRQoL) assessed with the European Quality of life - 5 Dimensions - 3 Levels (EQ-5D-3L) questionnaire, a standardized validated questionnaire administered in Danish. The EQ-5D-3L questionnaire comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. |
| Number of treatment-related adverse events as assessed by CTCAE v5.0 | From baseline to month 6. | Safety and tolerance of oral semaglutide treatment in patients with glaucoma assessed by the incidence of treatment-emergent adverse events (TEAEs) by CTCAE v5.0. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Optical coherence tomography (OCT), macular scan | From baseline to month 6. | Structural glaucoma progression assessed by the OCT macular scan which measures the volume of retinal ganglion cells. |
| Standard automated perimetry | From baseline to month 6. | Visual field loss will be evaluated using standard automated perimetry. Progression will be measured by changes in mean deviation (MD). |
| Multi-omics | From baseline to month 6. | Changes in the cytokine proteome will be assessed by changes in concentrations of glaucoma-associated cytokines as related to inflammation. Changes in the metabolome and lipidome will be assessed by changes in plasma metabolomics and lipidomics. |
| Optical coherence tomography (OCT), ring scan | From baseline to month 6. | Structural glaucoma progression assessed by the OCT ring scan, which measures the retinal nerve fibre layer thickness. |
Countries
Denmark
Contacts
Primary ContactMiriam Kolko, MD, PhD
Backup ContactAnna-Sophie Thein
Outcome results
None listed