Unprescrib-D

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Hovedstaden

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Decision date (initial)

2026-06-29

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Mental Health Services - Capital Region of Denmark · The Lundbeck Foundation · Independent Research Fund Denmark · Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objectives are to determine if COC discontinuation (COCd) compared with COC continuation (COCc) affects (i) antidepressant treatment outcome and (ii) verbal memory performance at week 8 under concomitant pharmacological antidepressant treatment.

Secondary objectives 18

1. To determine if COCd compared with COCc will affect pharmacological antidepressant treatment titration rank at week 8, as measured by the required antidepressant dose/add-on/switches to alternative or adjunctive antidepressant therapies
2. To determine if COCd compared with COCc will result in better clinical recovery at week 1, 2, 4, and 12 under concomitant pharmacological antidepressant treatment
3. To determine if COCd compared with COCc will result in better verbal memory performance at week 4 and 12 under concomitant pharmacological antidepressant treatment
4. Domain-specific objective 1: To determine if COCd compared with COCc will result in higher striatal 5-HT4R binding after 8 weeks of pharmacological antidepressant treatment
5. Domain-specific objective 2: To determine if 8 weeks of pharmacological antidepressant treatment will result in higher peripheral and brain insulin sensitivity and if this will be more pronounced in COCd compared with COCc
6. Domain-specific objective 3: To determine if COCd compared with COCc will result in greater cortisol dynamics at week 8 under concomitant pharmacological antidepressant treatment
7. Domain-specific objective 4: To determine if COCd compared with COCc will result in lower peripheral and brain inflammation at week 8 under concomitant pharmacological antidepressant treatment
8. Domain-specific objective 5: To determine if COCd compared with COCc will result in higher hippocampal activation during memory encoding at week 8 under concomitant pharmacological antidepressant treatment
9. Domain-specific objective 6a: To determine if COCd compared with COCc will result in more sexual desire at week 8 under concomitant pharmacological antidepressant treatment
10. Domain-specific objective 6b: To determine if COCd compared with COCc will result in higher reward-related activation of ventral striatum at week 8 under concomitant pharmacological antidepressant treatment
11. Domain-specific objective 7: To determine if COCd compared with COCc will result in less anxiety at week 8 under concomitant pharmacological antidepressant treatment
12. Domain-specific objective 8: To determine if COCd compared with COCc will result in an altered resting state functional connectivity at week 8 under concomitant pharmacological antidepressant treatment
13. Domain-specific objective 9: To determine if COCd compared with COCc will result in higher hippocampal volume at week 8 under concomitant pharmacological antidepressant treatment
14. Domain-specific objective 10: To determine if COCd compared with COCc will result in an altered gut microbiome and gut microbiota-derived metabolite composition at week 8 under concomitant pharmacological antidepressant treatment
15. Domain-specific objective 11: To determine if COCd compared with COCc will result in better sleep at week 8 under concomitant pharmacological antidepressant treatment
16. Domain-specific objective 12a: To determine if COCd compared with COCc will result in fewer depressive symptoms and lower treatment titration rank 6 months after start of the intervention
17. Domain-specific objective 12b: To determine if COCd compared with COCc will result in higher probability of remission 6 months after start of the intervention
18. Domain-specific objective 12c: To determine if COCd compared with COCc will result in a lower risk of hospitalization, suicide, suicide attempt, or treatment switches/add-on within 12 months after start of the intervention

Conditions and MedDRA coding

Major Depressive Disorder

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Female biological sex
2. Age 18-39 years
3. Current user of combined oral contraception, which was started at least one month prior to inclusion
4. Fulfillment of ICD-10 for primary moderate to severe unipolar depressive episode (i.e., not secondary to organic or other psychiatric disorder), for which treatment with SSRI monotherapy is clinically indicated.

Exclusion criteria 19

1. Acute suicidality
2. Prior or current schizophrenia diagnosis or psychosis/psychotic symptoms
3. Alcohol and substance use disorders
4. Other psychiatric disorder requiring other treatments than SSRI
5. Contraindication for use of sertraline and duloxetine
6. Other current antidepressant treatment, including psychotherapy, than sertraline
7. Use of sertraline for more than 1 month at inclusion
8. Other antidepressant drug treatment attempt in current depressive episode
9. Known non-responder to SSRI
10. Duration of depressive episode exceeding 2 years
11. Severe somatic disease or traumatic brain injury
12. Pregnancy or breastfeeding or any plan to become pregnant within the next 3 months
13. Menopause, perimenopause or use of hormonal replacement therapy
14. Insufficient Danish language skills to complete cognitive and psychometric testing
15. Contraindication for use of Femicept
16. Moderate to severe gynecological conditions in which COCs are recommended as standard treatment, including endometriosis, severe dysmenorrhea, severe acne, menorrhagia associated with anemia, and polycystic ovary syndrome.
17. Additional exclusion criteria for participants volunteering for MRI and MRI/PET scan program: Contraindications for MRI (e.g. metal implants or claustrophobia)
18. Additional exclusion criteria for participants volunteering for MRI/PET scan program: Participation in experiments with exposure to radioactivity (> 10 mSv) within the last year of significant occupational exposure to radioactivity (only participants volunteering for the MRI/PET scan program)
19. Additional exclusion criteria for participants volunteering for MRI and MRI/PET scan program: Use of prescription drugs with known serotonergic effects within 2 months of inclusion, including sertraline and other antidepressants

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The mean Hamilton Depressive Rating Scale 6-item (HRDS-6) score
2. The mean total Verbal Affective Memory Task 24 (VAMT-24) recall score calculated as the average score across the immediate (0-24), short- (0-24), and long-term (0-24) recall

Secondary endpoints 25

1. Antidepressant treatment titration rank as defined in the protocol
2. Mean HRDS-6 score
3. The mean total Rey- Auditory Verbal Learning Test (RAVLT) recall score calculated as the average score across the immediate (0-15), short- (0-15), and long-term (0-15) recall
4. Domain-specific end point 1: Mean striatal 5-HT4R non-displaceable binding potential (BPND) as measured by positron emission tomography
5. Domain-specific end point 2a: Mean hypothalamic blood flow response to oral glucose as a proxy for brain insulin sensitivity
6. Domain-specific end point 2b: Mean hypothalamic blood-oxygen-level-dependent response to oral glucose
7. Domain-specific end point 2c: Mean Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) as a measure for peripheral insulin sensitivity
8. Domain-specific end point 3: Mean cortisol awakening response
9. Domain-specific end point 4a: Mean extra-neurite mean diffusivity as a proxy for brain inflammation
10. Domain-specific end point 4b: Mean hcCRP as a measure of peripheral inflammation
11. Domain-specific end point 4c: kynurenic acid/quinolinic acid ratio (neuroprotective index)
12. Domain-specific end point 5: Mean hippocampal activation as measured by functional magnetic resonance imaging (fMRI) during a memory encoding paradigm
13. Domain-specific end point 6a: Mean Element of Desire score
14. Domain-specific end point 6b: Mean ventral striatal activation as measured by fMRI during a monetary reward paradigm
15. Domain-specific end point 7: Mean General Anxiety Disorder-7 score
16. Domain-specific end point 8: Mean resting state functional connectivity as measured with resting state fMRI
17. Domain-specific end point 9: Mean hippocampal gray matter volume as measured with magnetic resonance imaging (MRI)
18. Domain-specific end point 10a: Gut microbiome composition
19. Domain-specific end point 10b: Mean gut microbiome-derived metabolites
20. Domain-specific end point 11: Mean Pittsburgh Sleep Quality Index score
21. Domain-specific end point 12a: Mean Major Depression Inventory (MDI) score
22. Domain-specific end point 12b: Mean HRDS-6 score
23. Domain-specific end point 12c: Treatment titration rank (defined in the protocol)
24. Domain-specific end point 12d: Time to remission
25. Domain-specific end point 12e: Time to hospitalization, suicide, suicide attempt, or treatment switches/add-on

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Hovedstaden

Sponsor organisation

Region Hovedstaden

Address

Nordre Fasanvej 57

City

Frederiksberg

Postcode

2000

Country

Denmark

Scientific contact point

Organisation

Region Hovedstaden

Contact name

Søren Vinther Larsen

Public contact point

Organisation

Region Hovedstaden

Contact name

Søren Vinther Larsen

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications