hCG Treatment for Rehabilitation From a TBI (COGNI-REHAB)

VA Office of Research and Development

Status and phase: Begins enrollment this month; Early Phase 1

Conditions: Traumatic Brain Injury

Treatments: Drug: Ovidrel; Other: Placebo

Study type: Interventional

Funder types: Other U.S. Federal agency

Identifiers

NCT07557615

RRD1-026-25M

14343177 (Other Grant/Funding Number)

Details and patient eligibility

About

The COGNI-REHAB Trial is a single-site, phase O/I, randomized, double-blind, placebo-controlled study of human chorionic gonadotropin (hCG; choriogonadotropin alfa, Ovidrel®) in men with post-acute, moderate to severe traumatic brain injury (msTBI). Its objective is to assess the safety and efficacy of a 24-week regimen of Ovidrel (125 micrograms twice weekly) compared to placebo on treatment-emergent adverse events (TEAEs), cognitive and functional recovery, and circulating sex hormones.

Full description

This project aims to re-purpose a safe, well-tolerated, already-approved medication: human chorionic gonadotropin (hCG; choriogonadotropin alfa, Ovidrel®) for use in the post-acute rehabilitation of moderate to severe traumatic brain injury (msTBI). Ovidrel is currently FDA-approved for use in ovulation induction and Assisted Reproductive Technologies (ART). The rationale for using Ovidrel comes from a convergence of evidence indicating that hCG has neurodevelopmental and neuroregenerative properties, and from preclinical studies demonstrating that hCG reverses TBI-induced suppression of sex hormone production (i.e., reverses hypogonadism) and improves recovery of sensorimotor and spatial learning and memory in rodents following a focal injury to the medial prefrontal cortex. Recovery from a TBI is typically a very slow process because innate neuronal regeneration is a slow process; thus, Ovidrel (125 µg twice weekly) treatment will be evaluated over 24-weeks in patients that are 1-6 months post-TBI.

Enrollment: 50 estimated patients

Sex: Male

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male subjects aged 18-65
• Subject is 1-month but < 6-month post-TBI with a msTBI defined as Glasgow Coma Scale (GCS) 4-12 (inclusive) at the time of the TBI, and/or at the time of screening (Visit 1)
• Stable doses of any medication, supplement or medical food that may affect brain function, unless deemed medically necessary by the patient's physician for optimal healthcare
• Fluent in English
• Reasonable expectation of availability to receive the 24-week course of therapy and be available for follow up evaluations

Exclusion criteria

• Significantly depressed (Geriatric Depression Scale > 10)
• Patients considered to be at risk for suicidality or homicidality according to the Columbia Suicide Severity Rating Scale (CSSRS)
• Primary hypogonadism (unrelated to trauma)
• Renal disease; Asthma; known endocrine or germ cell tumor
• Taking other medications known to affect serum sex hormone or gonadotropin concentrations such as testosterone for hormone replacement therapy, goserelin or danazol, in the past three (3) months
• Presence of significant systemic illness likely to interfere with participation in or completion of the study or to affect study results
• Receiving other investigational drugs within 30 d or 5 half-lives prior to randomization, whichever longer
• Male patients with known/documented elevated PSA levels, or a PSA level of 4ng/mL at screening
• History of deep venous thrombosis (DVT) or venous thromboembolism (VTE)
• Clinically significant peripheral edema
• History of sleep apnea
• Severe symptoms of benign prostatic hyperplasia (BPH), i.e., International Prostate Symptom Score greater than or equal to 20 points
• Patients with known hypercoagulability, including cardiolipin/antiphospholipid antibody syndrome
• Allergy or other contraindication to hCG
• Uncontrolled hypertension, defined as blood pressure persistently above 140 mm Hg systolic or 95 mm Hg diastolic despite antihypertensive therapy
• Uncontrolled thyroid, adrenal or pituitary dysfunction
• An uncontrolled organic intracranial lesion such as a pituitary tumor
• History of breast or prostate cancer; sex hormone dependent tumors of the reproductive organs or accessory sex glands
• Taking hCG, or any condition known to elevate hCG, active in the prior 24 mo. e.g., choriocarcinoma or germ cell tumor
• Patients who have 6 or more symptoms for substance use disorder according to DSM-5 criteria
• Patients with evidence of an active or previous thrombotic event

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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50 participants in 2 patient groups, including a placebo group

Treatment Arm

Experimental group

Description:

Ovidrel: 125 micrograms in 0.25 mL administered subcutaneously twice weekly for 24 weeks

Treatment:

Drug: Ovidrel

Placebo Arm

Placebo Comparator group

Description:

Placebo: 0.25 mL of sterile normal saline administered subcutaneously twice weekly for 24 weeks

Treatment:

Other: Placebo