Trial of sertraline to prevent post-traumatic brain injury depressio

Phase 3

• Conditions: Depressive disorder after traumatic brain injury; Mental and Behavioural Disorders

• Registration Number: ISRCTN17518945
• Lead Sponsor: King's College Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-12-23
• Last Update Posted: 21 May 2024
• Study Completion: 2025-04-30

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 514

Inclusion Criteria

Participant inclusion criteria as of 29/04/2024:
1. Adults aged 18 years and above
2. UK residents
3. Possible, mild or moderate-severe TBI that occurred less than 8 weeks before time of consent defined as possible, probable and definite TBIs by the Mayo Classification System
4. No current major depressive disorder as measured by the Structured Clinical Interview (SCID)

Previous participant inclusion criteria:
1. Adults aged 18 years and above
2. UK residents
3. Mild or moderate-severe TBI that occurred less than 4 weeks before time of consent defined as probable and definite TBIs by the Mayo Classification System
4. No current major depressive disorder as measured by the Structured Clinical Interview (SCID)

Exclusion Criteria

Participant exclusion criteria as of 29/04/2024:
1. Concurrent antidepressant medication at the British National Formulary recommended therapeutic doses for the treatment of depression
2. Other causes of acquired brain injury such as stroke
3. Known psychotic or bipolar disorders (except for mild cognitive impairment), known dementia (except for mild), actively suicidal, other acute or chronic neurological conditions except post-traumatic epilepsy, terminal or advanced medical illness such as end-stage kidney failure, heart failure, severe hepatic impairment
4. Pregnant or planning pregnancy
5. Women of childbearing potential if they are not using acceptable effective methods of contraception as defined by the Clinical Trials Facilitation Group (CTFG) (a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. For the purpose of this document, a man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy.)
Female subjects must agree to one of the following during the duration of the study:
5.1. Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable method of contraception only when it is in line with the subject’s preferred and usual lifestyle.
5.2. Consistent and correct use of 1 of the following methods of birth control: a) intrauterine device (IUD) with a failure rate of <1% per year; b) tubal sterilization; c) vasectomy in the male partner; d) hormonal methods (oral contraceptives, injectable progesterone, implants of levonorgestrel, transdermal contraceptive patch, contraceptive vaginal ring). In the case of the Essure micro-insert system, this will need to be used in association with another method of contraception; Male subjects with female partners of childbearing potential must use condoms during the trial.
6. Lactating
7. Medical causes of depression such as pituitary failure
8. Known allergy to sertraline
9. Current hyponatraemia (if participant’s sodium is <135 mmol/L it will be discussed with the site PI or their treating physician to confirm it is safe for the patient to be enrolled)
10. Taking medications contraindicated with sertraline as stated in the SmPC including concomitant treatment with irreversible monoamine oxidase inhibitors and pimozide
11. Participating in another CTIMP study or participated <=30 days from consent
12. Participants will be excluded if they are not able to complete self-administered questionnaires in English. (English proficiency in comatose patients will be assessed through next of kin and to the best of the ability of the clinician with the available information. Participants who come out of a coma will be reassessed for eligibility regarding English proficiency criterion. If non-proficient in English, they will be withdrawn.)

Previous participant exclusion criteria:
1. Possible TBI according to the Mayo Classification System
2. Concurrent

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Depressive symptoms measured by Patient Health Questionnaire-9 (PHQ-9) score collected at baseline, 6, 12 and 18 months. The primary outcome will be formally assessed at 12 months.