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

April 30, 2026 updated by: VA Office of Research and Development

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Wisconsin
      • Madison, Wisconsin, United States, 53705-2254
        • William S. Middleton Memorial Veterans Hospital, Madison, WI
        • Contact:
        • Contact:
        • Principal Investigator:
          • Craig Atwood, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment Arm
Ovidrel: 125 micrograms in 0.25 mL administered subcutaneously twice weekly for 24 weeks
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), and Water for Injection to deliver 125 micrograms of choriogonadotropin alfa in 0.25 mL twice weekly. The pH of the solution is 6.5 to 7.5.
Other Names:
  • Choriogonadotropin alfa
Placebo Comparator: Placebo Arm
Placebo: 0.25 mL of sterile normal saline administered subcutaneously twice weekly for 24 weeks
Other: Placebo
Prefilled syringe of 0.250 mL normal saline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent change in Treatment-Emergent Adverse Events
Time Frame: Baseline, 26 Weeks
The frequency and type of individual TEAEs, discontinuations due to TEAEs, serious TEAEs, and clinically significant changes in laboratory test values.
Baseline, 26 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent change in modified Functional Independence Measure (FIM)
Time Frame: Baseline, 24 Weeks
The FIM is a standardized rating of motor and cognitive disability is commonly used to guide and track progress during rehabilitation, drilling down into level of assistance required for various daily tasks.
Baseline, 24 Weeks
Glasgow Outcome Scale-Extended (GOSE)
Time Frame: Baseline, 24 Weeks
The GOSE is a brief standardized tool developed for assessing TBI severity and recovery, offering a useful global indicator of disability severity.
Baseline, 24 Weeks
Percent Change in Neuropsychiatric Inventory (NPI)
Time Frame: Baseline, 24 Weeks
The NPI measures psychopathology in patients with neurological disorders, this tool allows brief screening of different conditions. When a screening item is positive, it follows up with more detail of symptom types, frequency, severity, and how distressing it is to caregivers. This makes for a very efficient and useful tool, providing a more comprehensive assessment of symptoms when they are present, and can be used to track recovery.
Baseline, 24 Weeks
Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5)
Time Frame: Baseline, 24 Weeks
This standardized self-rated scale detects presence and severity of PTSD symptoms and is used for monitoring during recovery. This is widely used in the veteran TBI literature as PTSD is frequently comorbid with TBI and can complicate recovery. This is a necessary complement to the NPI, which doesn't assess PTSD.
Baseline, 24 Weeks
Percent change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Time Frame: Baseline, 24 Weeks
RBANS is used in msTBI to assess cognitive impairment and track recovery in rehabilitation, this performance-based test generates a Total cognition score, which is made up of indices of Attention, Learning, Memory, Language, and Visuospatial skills. Each index can be broken down into two or more different aspects of the given cognitive domain. This allows for both global and more fine-grained analysis of cognitive impairment and recovery.
Baseline, 24 Weeks
Percent change in Automated Neuropsychological Assessment Metrics Military (ANAM)
Time Frame: Baseline, 24 Weeks
ANAM is used by the US military to assess cognitive function in service members for pre-deployment screening, post-injury monitoring, TBI detection and recovery. This test complements the RBANS by offering a measure of reaction time and more robust assessment of processing speed and executive functions.
Baseline, 24 Weeks
Percent change in Trail Making Test (TMT)
Time Frame: Baseline, 24 Weeks
TMT is a test of simple psychomotor speed and complex attention / executive control. It requires less manual dexterity than the RBANS and is less complicated by reaction time than the ANAM, so is useful in a mixed msTBI population as some participants may also have motor disability.
Baseline, 24 Weeks
Columbia-Suicide Severity Rating Scale (C-SSRS)
Time Frame: Baseline, 26 Weeks
The "Columbia Protocol" is a brief tool used by healthcare professionals to identify if a person is at risk for suicide.
Baseline, 26 Weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Circulating Sex Hormone Concentrations
Time Frame: Baseline, 26 Weeks
Percent change in circulating sex hormone concentrations.
Baseline, 26 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Investigators

  • Principal Investigator: Craig Atwood, PhD, William S. Middleton Memorial Veterans Hospital, Madison, WI

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2026

Primary Completion (Estimated)

July 1, 2029

Study Completion (Estimated)

September 30, 2029

Study Registration Dates

First Submitted

April 22, 2026

First Submitted That Met QC Criteria

April 22, 2026

First Posted (Actual)

April 29, 2026

Study Record Updates

Last Update Posted (Actual)

May 6, 2026

Last Update Submitted That Met QC Criteria

April 30, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RRD1-026-25M
  • 14343177 (Other Grant/Funding Number: 1I02RD000527-01P1)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The data and resources sharing plan for this project is in accordance with the Veterans Administration Data Sharing Policies. All raw clinical, genetic, and imaging data from this project will be available upon written request. Deidentified data may be uploaded to one or more of several available data sharing sites designed for this purpose. The final data will be available in acceptable formats such as presentations and publications.

Research data and results that document and support the study aims will be available after the final results are accepted for publication. The data to be shared will be anonymized and there will be no fees or other restrictions.

IPD Sharing Time Frame

Research data and results that document and support the study aims will be available after the final results are accepted for publication.

IPD Sharing Access Criteria

Approval from PI

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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