Traumatic Brain InjuryEarly Phase 1COGNI-REHABNCT07557615
hCG Treatment for Rehabilitation From a TBI
A Early Phase 1 study testing Ovidrel in people with Traumatic Brain Injury, run by VA Office of Research and Development at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 65 years, men only
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Ovidrel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2027to 31 Dec 2029
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is 1-month but < 6-month post-traumatic brain injury (TBI) with a moderate to severe traumatic brain injury (msTBI) defined as Glasgow Coma Scale (GCS) 4-12 (inclusive) at the time of the traumatic brain injury (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
Who cannot join
- 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
Show all 21Show fewer
- 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 human chorionic gonadotropin (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 human chorionic gonadotropin (hCG), or any condition known to elevate human chorionic gonadotropin (hCG), active in the prior 24 months, 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
William S. Middleton Memorial Veterans Hospital, Madison, WI
Madison, Wisconsin, 53705-2254
Jenna W Quinto, PhD, (680) 256-1901 ext. 17865, jenna.quinto@va.gov
Aaron F Heneghan, PhD, (608) 256-1901 ext. 17801, Aaron.Heneghan@va.gov
About this study
Official title: 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.
Read the 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.
- Conditions
- Traumatic Brain Injury
- Being tested
- Ovidrel, Placebo
- Keywords
- Traumatic brain injury, Human chorionic gonadotropin
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OvidrelDrug
Also called Choriogonadotropin alfa
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 milliliters (mL) containing 257.5 micrograms of choriogonadotropin alfa, 28.1 milligrams (mg) mannitol, 505 grams (g) 85% O-phosphoric acid, 103 grams (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 milliliters (mL) twice weekly. The pH of the solution is 6.5 to 7.5.
PlaceboOther
Prefilled syringe of 0.250 milliliters (mL) normal saline.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Ovidrel: 125 micrograms in 0.25 milliliters (mL) administered subcutaneously twice weekly for 24 weeks Receives: Drug: Ovidrel |
| Placebo Arm | Placebo comparator | Placebo: 0.25 milliliters (mL) of sterile normal saline administered subcutaneously twice weekly for 24 weeks Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change in Treatment-Emergent Adverse Events
The frequency and type of individual TEAEs, discontinuations due to TEAEs, serious TEAEs, and clinically significant changes in laboratory test values.
Measured: Baseline, 26 Weeks
Secondary outcomes (8)
Percent change in modified Functional Independence Measure (FIM)
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.
Measured: Baseline, 24 Weeks
Glasgow Outcome Scale-Extended (GOSE)
The GOSE is a brief standardized tool developed for assessing TBI severity and recovery, offering a useful global indicator of disability severity.
Measured: Baseline, 24 Weeks
Percent Change in Neuropsychiatric Inventory (NPI)
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.
Measured: Baseline, 24 Weeks
Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5)
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.
Measured: Baseline, 24 Weeks
Percent change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
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.
Measured: Baseline, 24 Weeks
Percent change in Automated Neuropsychological Assessment Metrics Military (ANAM)
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.
Measured: Baseline, 24 Weeks
Percent change in Trail Making Test (TMT)
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.
Measured: Baseline, 24 Weeks
Columbia-Suicide Severity Rating Scale (C-SSRS)
The "Columbia Protocol" is a brief tool used by healthcare professionals to identify if a person is at risk for suicide.
Measured: Baseline, 26 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2026
- Study start1 Jan 2027 (estimated)
- Primary completion1 Oct 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Placebo controlled.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Craig Atwood, PhD, Principal investigator, William S. Middleton Memorial Veterans Hospital, Madison, WI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07557615
- Sponsor's protocol ID
- RRD1-026-25M
- Other IDs
- 14343177
- Acronym
- COGNI-REHAB
- Status last verified
- Oct 2026
- First submitted
- 22 Apr 2026
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
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. eCollection 2021 Jul.
PubMed 34277964
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chorionic Gonadotropin to Improve Rehabilitation After Brain Injury - The COGNI-REHAB Study
- ClinicalTrials.gov ID
- NCT07557615
- Acronym / sponsor ID
- COGNI-REHAB / RRD1-026-25M
- Conditions
- Traumatic Brain Injury
- Keywords
- Traumatic brain injury, Human chorionic gonadotropin
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- 1 Oct 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 29 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Placebo controlled.
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: OvidrelOvidrel: 125 micrograms in 0.25 milliliters (mL) administered subcutaneously twice weekly for 24 weeks |
| Placebo Arm | Placebo comparator | Other: PlaceboPlacebo: 0.25 milliliters (mL) of sterile normal saline administered subcutaneously twice weekly for 24 weeks |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Subject is 1-month but < 6-month post-traumatic brain injury (TBI) with a moderate to severe traumatic brain injury (msTBI) defined as Glasgow Coma Scale (GCS) 4-12 (inclusive) at the time of the traumatic brain injury (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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OvidrelAlso: Choriogonadotropin alfaOvidrel, 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 milliliters (mL) containing 257.5 micrograms of choriogonadotropin alfa, 28.1 milligrams (mg) mannitol, 505 grams (g) 85% O-phosphoric acid, 103 grams (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 milliliters (mL) twice weekly. The pH of the solution is 6.5 to 7.5. | Drug | Treatment Arm |
| PlaceboPrefilled syringe of 0.250 milliliters (mL) normal saline. | Other | Placebo Arm |
Primary outcome
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.
8 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.
- Background: PubMed 34277964Geddes 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. eCollection 2021 Jul.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Craig Atwood, PhD principal investigator
William S. Middleton Memorial Veterans Hospital, Madison, WI
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Ovidrel in people with Traumatic Brain Injury, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Craig Atwood, PhD ((608) 280-7000 ext. 13326, Craig.Atwood@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent change in Treatment-Emergent Adverse Events (time frame: Baseline, 26 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07557615, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.