hCG Treatment for Rehabilitation From a TBI

Official title

Chorionic Gonadotropin to Improve Rehabilitation After Brain Injury - The COGNI-REHAB Study

Overview

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.

Detailed 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.

Interventions

• Drug Ovidrel
  Ovidrel, recombinant human chorionic gonadotropin, comes in a prefilled syringe for subcutaneous injection, is the investigational agent that will be used in this trial. Ovidrel® PreFilled Syringe is a sterile, liquid intended for subcutaneous (s.c.) injection. Each Ovidrel® PreFilled Syringe is filled with 0.515 mL containing 257.5 micrograms of choriogonadotropin alfa, 28.1 mg mannitol, 505 g 85% O-phosphoric acid, 103 g L-methionine, 51.5 g Poloxamer 188, Sodium Hydroxide (for pH adjustment),
• Other Placebo
  Prefilled syringe of 0.250 mL normal saline.

Primary outcome measures

• Percent change in Treatment-Emergent Adverse Events [Time frame: Baseline, 26 Weeks]

Secondary outcome measures (8)

• Percent change in modified Functional Independence Measure (FIM) [Time frame: Baseline, 24 Weeks]
• Glasgow Outcome Scale-Extended (GOSE) [Time frame: Baseline, 24 Weeks]
• Percent Change in Neuropsychiatric Inventory (NPI) [Time frame: Baseline, 24 Weeks]
• Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) [Time frame: Baseline, 24 Weeks]
• Percent change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [Time frame: Baseline, 24 Weeks]
• Percent change in Automated Neuropsychological Assessment Metrics Military (ANAM) [Time frame: Baseline, 24 Weeks]
• Percent change in Trail Making Test (TMT) [Time frame: Baseline, 24 Weeks]
• Columbia-Suicide Severity Rating Scale (C-SSRS) [Time frame: Baseline, 26 Weeks]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• William S. Middleton Memorial Veterans Hospital, Madison, WI — Madison

Publications

• Geddes RI, Kapoor A, Hayashi K, Rauh R, Wehber M, Bongers Q, Jansen AD, Anderson IM, Farquhar G, Vadakkadath-Meethal S, Ziegler TE, Atwood CS. Hypogonadism induced by surgical stress and brain trauma is reversed by human chorionic gonadotropin in male rats: A potential therapy for surgical and TBI-induced hypogonadism? Endocrinol Diabetes Metab. 2021 Mar 18;4(3):e00239. doi: 10.1002/edm2.239. eCol PMID 34277964

Identifiers

NCT: NCT07557615 · RRD1-026-25M · 14343177

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗