Vegetative StatePhase 2NCT07918274
Restoring Awareness
A Phase 2 study testing Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93) in people with Vegetative State and Minimally Conscious State, run by Casa Colina Hospital and Centers for Healthcare.
Trial summary
The study will evaluate the safety and preliminary efficacy of saxagliptin in treating prolonged DoC through a randomized, placebo-controlled, double-blind, delayed start Phase IIA trial. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Vegetative State, Minimally Conscious State
- What is being tested?
- Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- No sites listed yet
- Study dates
- 15 Nov 2026to 30 Oct 2030
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Any etiology: traumatic brain injury, anoxic brain injury, or vascular (stroke) brain injury.
- Enrolled at Casa Colina Hospital's Center for Disorders of Consciousness (C³DoC).
- Legally authorized representative (LAR) available to provide informed consent.
- Medically stable for participation as determined by the Clinical Co-Investigator (Dr. David Patterson, MD).
Who cannot join
- Type I or Type II Diabetes Mellitus.
- Current use of strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) due to potential saxagliptin exposure increase.
- Current use of insulin or insulin secretagogues.
- Heart failure of NYHA Class II-IV, active decompensated heart failure, or hospitalization for heart failure within 12 months before screening. Because NYHA class is defined by symptoms during physical exertion and cannot be assessed in patients with disorders of consciousness, any patient with a documented diagnosis of heart failure is excluded unless the medical record documents NYHA Class I status before the qualifying brain injury and there has been no subsequent heart failure decompensation or hospitalization.
- Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m², calculated from the screening serum creatinine using the CKD-EPI 2021 equation (Inker et al., 2021). Because reduced muscle mass after prolonged immobility can cause creatinine-based eGFR to overestimate renal function, the Clinical Co-Investigator may additionally obtain a cystatin C-based eGFR; a patient is excluded if either estimate is <60 mL/min/1.73 m².
- Known hypersensitivity to saxagliptin or any DPP-4 inhibitor, or a history of angioedema.
Show all 10Show fewer
- History of pancreatitis or bullous pemphigoid.
- Unstable vital signs, active infections, or recent hospitalizations for acute medical illness.
- Pregnancy or lactation.
- Any condition that, in the judgment of the investigator, would make the patient unsuitable for participation.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Restoring Awareness in Prolonged Disorders of Consciousness With Drug Recycling
The study will evaluate the safety and preliminary efficacy of saxagliptin in treating prolonged DoC through a randomized, placebo-controlled, double-blind, delayed start Phase IIA trial. Twenty-four (24) patients with prolonged DOC (≥28 days post-injury) will be enrolled at Rehabilitation Hopsital's Center for Disorders of Consciousness (C³DoC).
Twelve patients will be randomized to receive placebo for 15 days followed by saxagliptin 5 mg for 15 days (Delayed Start Group), and 12 will receive saxagliptin 5 mg for the full 30 days (Full Treatment Group). Patients will be under continuous medical monitoring within C³DoC throughout their approximately 4-week admission. Validated behavioral biomarkers of consciousness (CRS-R) will be collected by blinded certified assessors at baseline (days -7 and 0), day 15, and day 30, with portable EEG-based AI biomarker assessments to corroborate behavioral findings. Follow-up DRS-PI assessments will be conducted at days 60 and 90.
A pre-planned adaptive dose escalation design will be employed. The first 6 patients (sentinel cohort) will receive 5 mg (or placebo per delayed start). Upon cohort completion, the independent Safety Monitoring Board (SMB), chaired by a Medical doctor , will review unblinded safety data. If IRB and FDA IND Exemption approval is obtained for dose escalation, and excellent safety criteria are met (zero SAEs, no Grade 2+ AEs, zero hypoglycemia), the SMB will direct escalation to 10 mg for subsequent patients (up to 400 mg/day has been shown to be well-tolerated in humans); otherwise, 5 mg continues. Investigators and patients remain blinded throughout.
Read the detailed description
When individuals suffer a severe brain injury and do not completely regain their previous functional abilities, frequently develop a Disorder of Consciousness (DoC). This refers to a collection of interconnected conditions characterized by reduced awareness and alertness, such as the Vegetative State (VS) and the Minimally Conscious State(MCS). When these conditions persist over time, there are currently no authorized pharmacological interventions available to enhance their recovery. Only one medication, amantadine, has Class II evidence for DOC, offering modest benefit with no group difference versus placebo at trial end . Eight drugs, which are indicated for other conditions, have previously shown some promise in improving alertness and awareness in some DoC patients. These drugs are amantadine, apomorphine, baclofen, bromocriptine, desipramine, levodopa, methylphenidate, and zolpidem. In order to identify new potential drugs for DoC, investigators trained a deep neural network to predict the efficacy of these eight drugs, as well as 288 other drugs known to be ineffective (from prior research and patient records), based on their molecular structure. This phenotypic AI screening was trained on both acute coma and prolonged DOC cases. Investigators then used this trained network to predict the efficacy of all other FDA-approved drugs in chronic DoC. This in silico drug screen identified a new, FDA-approved medication with promise in ameliorating chronic DoC: the type 2 diabetes medication saxagliptin. This finding has since been supported by a retrospective study of 4,047 ICU acute coma patients matched by age, sex, Glasgow Coma Scale score, etiology, and glycemic status, in which incretin-based therapies (including DPP-4 inhibitors) yielded significantly higher recovery rates versus non-incretin diabetes medications (P=0.0331), patients without diabetes (P=0.0272), and amantadine-treated patients (P=0.0364) (Toker et al., 2025). Recovery rates with incretin-based drugs were consistent across coma etiologies: TBI (76.5%), stroke (73.7%), and anoxic (74.9%); saxagliptin-treated patients showed 89% recovery. A new preclinical study also demonstrated saxagliptin significantly improved neurobehavioral outcomes and attenuated neuropathologies in severe TBI in non-diabetic rats .
In the present study, investigators propose to evaluate the safety and preliminary efficacy of saxagliptin in treating prolonged DoC through a randomized, placebo-controlled, double-blind, delayed start Phase IIA trial. Twenty-four (24) patients with prolonged DOC (≥28 days post-injury) will be enrolled at Rehabilitation Hospital's Center for Disorders of Consciousness (C³DoC).
Twelve patients will be randomized to receive placebo for 15 days followed by saxagliptin 5 mg for 15 days (Delayed Start Group), and 12 will receive saxagliptin 5 mg for the full 30 days (Full Treatment Group). Patients will be undercontinuous medical monitoring within C³DoC throughout their approximately 4-week admission. Validated behavioral biomarkers of consciousness (CRS-R) will be collected by blinded certified assessors at baseline (days -7 and 0), day 15, and day 30, with portable EEG-based AI biomarker assessments to corroborate behavioral findings. Follow-up DRS-PI assessments will be conducted at days 60 and 90. A pre-planned adaptive dose escalation design will be employed. The first 8 patients (sentinel cohort) will receive 5 mg (or placebo per delayed start). Upon cohort completion, the independent Safety Monitoring Board (SMB),chaired by a Medical Doctor, will review unblinded safety data. If IRB and FDA IND Exemption approval is obtained for dose escalation, and excellent safety criteria are met (zero SAEs, no Grade 2+ AEs, zero hypoglycemia), the SMB will direct escalation to 10 mg for only the remaining 6 patients in the full treatment arm; All 12 Delayed-Start patients will remain at 5 mg during active treatment (up to 400 mg/day has been shown to be well-tolerated in humans); otherwise, 5 mg continues. Investigators and patients remain blinded throughout. No confirmed adverse events of special interest (AESIs), no permanent study-drug discontinuations for safety reasons, completion of treatment and follow-up through Day 44 before escalation review.
- Conditions
- Vegetative State, Minimally Conscious State
- Being tested
- Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93)
- Keywords
- vegetative state, Minimally Conscious State
- Medical subject headings
- Persistent Vegetative State
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93)Drug
Days 16-30- administer 5 mg/day via G-tube
Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93)Drug
Days 1-30- administer 5 mg/day (or 10 mg/day per adaptive design) via G tube
| Study group | Role | What they receive |
|---|---|---|
| Delayed Start Group | Experimental | Placebo on days 1-15. Saxagliptin on days 16-30. Receives: Drug: Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93) |
| Full Treatment Group | Experimental | Saxagliptin given on days 1-30. Receives: Drug: Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93) |
| Placebo | No intervention | See delayed group information. Placebo will be given day 0-15 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of serious adverse events (SAEs)
Hypoglycemia (<70 mg/dL via continuous glucose monitoring), non-serious AEs (CTCAE v5.0), and discontinuations vs. placebo (first 15 days), and vitals.
Measured: From days 1-30
Change in CRS-R total score from baseline to Day 15 (placebo-controlled comparison) and Day 30.
CRS-R assessment divided into 6 subscales Total score ranging from 0-23. Higher scores indicate higher levels of neurological function and consciousness. Higher scores mean a better outcome.
Measured: Baseline, Days 15 and Days 30
Secondary outcomes (3)
CRS-R subscales
≥2-point increase or diagnostic advancement. DRS is out of 29 points (Scores range from 0 (no disability) to 29 (extreme vegetative state). Higher scores mean a better outcome.
Measured: Baseline, day 15, day 30
Portable EEG-based AI biomarker of consciousness level
A framework to decode consciousness level
Measured: Baseline, days 15, days 30
DRS-PI
The DRS-PI (Disability Rating Scale-Postacute Interview) is a standardized interview version of the Disability Rating Scale (DRS) designed for reliable telephone or direct administration with patients or proxy caregivers. Lower DRS-PI better outcome. Lower scores mean a better outcome.
Measured: Days 60 and Days 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2026
- Study start15 Nov 2026 (estimated)
- Primary completion30 Oct 2029 (estimated)
- Study completion30 Oct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Vegetative StateStudies of the same condition, open and under way.
- 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In the present study, we propose to evaluate the safety and preliminary efficacy of saxagliptin in treating prolonged DoC through a randomized, placebo-controlled, double-blind, delayed start Phase IIA trial. Twenty-four (24) patients with prolonged DOC (≥28 days post-injury) will be enrolled at Casa Colina's Center for Disorders of Consciousness (C³DoC). Twelve patients will be randomized to receive placebo for 15 days followed by saxagliptin 5 mg for 15 days (Delayed Start Group), and 12 will receive saxagliptin 5 mg for the full 30 days (Full Treatment Group). Patients will be under continuous medical monitoring within C³DoC throughout their approximately 4-week admission. Validated behavioral biomarkers of consciousness (CRS-R) will be collected by blinded certified assessors at baseline (days -7 and 0), day 15, and day 30, with portable EEG-based AI biomarker assessments to corroborate behavioral findings. Follow-up DRS-PI assessments will be conducted at days 60 and 90.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Casa Colina Hospital and Centers for Healthcare
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, Los Angeles
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07918274
- Sponsor's protocol ID
- SaxaDOC
- Status last verified
- Oct 2026
- First submitted
- 12 Oct 2026
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Turner-Stokes L, Dzingina M, Shavelle R, Bill A, Williams H, Sephton K. Estimated Life-Time Savings in the Cost of Ongoing Care Following Specialist Rehabilitation for Severe Traumatic Brain Injury in the United Kingdom. J Head Trauma Rehabil. 2019 Jul/Aug;34(4):205-214. doi: 10.1097/HTR.0000000000000473.
PubMed 30801440Toker D, Chiang JN, Vespa PM, Schnakers C, Monti MM. The Dipeptidyl Peptidase-4 Inhibitor Saxagliptin as a Candidate Treatment for Disorders of Consciousness: A Deep Learning and Retrospective Clinical Analysis. Neurocrit Care. 2025 Aug;43(1):101-118. doi: 10.1007/s12028-025-02217-0. Epub 2025 Feb 4.
PubMed 39904872TBI Model systems National Database (2016). Moderate to severe traumatic brain injury is a lifelong condition. https:// www.tbindsc.org/StaticFiles/Documents/CDC_NIDILRR_IAA_Policy.pdf.
Schnakers C, Monti MM. Disorders of consciousness after severe brain injury: therapeutic options. Curr Opin Neurol. 2017 Dec;30(6):573-579. doi: 10.1097/WCO.0000000000000495.
PubMed 28901969Pistoia F, Mura E, Govoni S, Fini M, Sara M. Awakenings and awareness recovery in disorders of consciousness: is there a role for drugs? CNS Drugs. 2010 Aug;24(8):625-38. doi: 10.2165/11535940-000000000-00000.
PubMed 20658796Paul D, Sanap G, Shenoy S, Kalyane D, Kalia K, Tekade RK. Artificial intelligence in drug discovery and development. Drug Discov Today. 2021 Jan;26(1):80-93. doi: 10.1016/j.drudis.2020.10.010. Epub 2020 Oct 21.
PubMed 33099022Pastores SM, Dakwar J, Halpern NA. Costs of critical care medicine. Crit Care Clin. 2012 Jan;28(1):1-10, v. doi: 10.1016/j.ccc.2011.10.003.
PubMed 22123095Monti MM. Cognition in the vegetative state. Annu Rev Clin Psychol. 2012;8:431-54. doi: 10.1146/annurev-clinpsy-032511-143050. Epub 2012 Jan 3.
PubMed 22224835Gray DS, Burnham RS. Preliminary outcome analysis of a long-term rehabilitation program for severe acquired brain injury. Arch Phys Med Rehabil. 2000 Nov;81(11):1447-56. doi: 10.1053/apmr.2000.16343.
PubMed 11083347Gosseries O, Demertzi A, Ledoux D, Bruno MA, Vanhaudenhuyse A, Thibaut A, Laureys S, Schnakers C. Burnout in healthcare workers managing chronic patients with disorders of consciousness. Brain Inj. 2012;26(12):1493-9. doi: 10.3109/02699052.2012.695426. Epub 2012 Jun 22.
PubMed 22725684Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil. 2004 Dec;85(12):2020-9. doi: 10.1016/j.apmr.2004.02.033.
PubMed 15605342Giacino JT, Ashwal S, Childs N, Cranford R, Jennett B, Katz DI, Kelly JP, Rosenberg JH, Whyte J, Zafonte RD, Zasler ND. The minimally conscious state: definition and diagnostic criteria. Neurology. 2002 Feb 12;58(3):349-53. doi: 10.1212/wnl.58.3.349.
PubMed 11839831Deacon CF, Holst JJ. Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. Adv Ther. 2009 May;26(5):488-99. doi: 10.1007/s12325-009-0030-9. Epub 2009 May 14.
PubMed 19444391Cullen NK, Park YG, Bayley MT. Functional recovery following traumatic vs non-traumatic brain injury: a case-controlled study. Brain Inj. 2008 Dec;22(13-14):1013-20. doi: 10.1080/02699050802530581.
PubMed 19117180Corso P, Finkelstein E, Miller T, Fiebelkorn I, Zaloshnja E. Incidence and lifetime costs of injuries in the United States. Inj Prev. 2015 Dec;21(6):434-40. doi: 10.1136/ip.2005.010983rep.
PubMed 26609059
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Restoring Awareness in Prolonged Disorders of Consciousness With Drug Recycling
- ClinicalTrials.gov ID
- NCT07918274
- Acronym / sponsor ID
- SaxaDOC
- Conditions
- Vegetative State, Minimally Conscious State
- Keywords
- vegetative state, Minimally Conscious State
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Casa Colina Hospital and Centers for HealthcareUniversity, hospital or other
- Collaborators
- University of California, Los Angeles
- Study start
- 15 Nov 2026 (estimated)
- Primary completion
- 30 Oct 2029 (estimated)
- Study completion
- 30 Oct 2030 (estimated)
- First posted
- 5 Nov 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 study will evaluate the safety and preliminary efficacy of saxagliptin in treating prolonged DoC through a randomized, placebo-controlled, double-blind, delayed start Phase IIA trial. Twenty-four (24) patients with prolonged DOC (≥28 days post-injury) will be enrolled at Rehabilitation Hopsital's Center for Disorders of Consciousness (C³DoC).
Twelve patients will be randomized to receive placebo for 15 days followed by saxagliptin 5 mg for 15 days (Delayed Start Group), and 12 will receive saxagliptin 5 mg for the full 30 days (Full Treatment Group). Patients will be under continuous medical monitoring within C³DoC throughout their approximately 4-week admission. Validated behavioral biomarkers of consciousness (CRS-R) will be collected by blinded certified assessors at baseline (days -7 and 0), day 15, and day 30, with portable EEG-based AI biomarker assessments to corroborate behavioral findings. Follow-up DRS-PI assessments will be conducted at days 60 and 90.
A pre-planned adaptive dose escalation design will be employed. The first 6 patients (sentinel cohort) will receive 5 mg (or placebo per delayed start). Upon cohort completion, the independent Safety Monitoring Board (SMB), chaired by a Medical doctor , will review unblinded safety data. If IRB and FDA IND Exemption approval is obtained for dose escalation, and excellent safety criteria are met (zero SAEs, no Grade 2+ AEs, zero hypoglycemia), the SMB will direct escalation to 10 mg for subsequent patients (up to 400 mg/day has been shown to be well-tolerated in humans); otherwise, 5 mg continues. Investigators and patients remain blinded throughout.
Detailed description
When individuals suffer a severe brain injury and do not completely regain their previous functional abilities, frequently develop a Disorder of Consciousness (DoC). This refers to a collection of interconnected conditions characterized by reduced awareness and alertness, such as the Vegetative State (VS) and the Minimally Conscious State(MCS). When these conditions persist over time, there are currently no authorized pharmacological interventions available to enhance their recovery. Only one medication, amantadine, has Class II evidence for DOC, offering modest benefit with no group difference versus placebo at trial end . Eight drugs, which are indicated for other conditions, have previously shown some promise in improving alertness and awareness in some DoC patients. These drugs are amantadine, apomorphine, baclofen, bromocriptine, desipramine, levodopa, methylphenidate, and zolpidem. In order to identify new potential drugs for DoC, investigators trained a deep neural network to predict the efficacy of these eight drugs, as well as 288 other drugs known to be ineffective (from prior research and patient records), based on their molecular structure. This phenotypic AI screening was trained on both acute coma and prolonged DOC cases. Investigators then used this trained network to predict the efficacy of all other FDA-approved drugs in chronic DoC. This in silico drug screen identified a new, FDA-approved medication with promise in ameliorating chronic DoC: the type 2 diabetes medication saxagliptin. This finding has since been supported by a retrospective study of 4,047 ICU acute coma patients matched by age, sex, Glasgow Coma Scale score, etiology, and glycemic status, in which incretin-based therapies (including DPP-4 inhibitors) yielded significantly higher recovery rates versus non-incretin diabetes medications (P=0.0331), patients without diabetes (P=0.0272), and amantadine-treated patients (P=0.0364) (Toker et al., 2025). Recovery rates with incretin-based drugs were consistent across coma etiologies: TBI (76.5%), stroke (73.7%), and anoxic (74.9%); saxagliptin-treated patients showed 89% recovery. A new preclinical study also demonstrated saxagliptin significantly improved neurobehavioral outcomes and attenuated neuropathologies in severe TBI in non-diabetic rats .
In the present study, investigators propose to evaluate the safety and preliminary efficacy of saxagliptin in treating prolonged DoC through a randomized, placebo-controlled, double-blind, delayed start Phase IIA trial. Twenty-four (24) patients with prolonged DOC (≥28 days post-injury) will be enrolled at Rehabilitation Hospital's Center for Disorders of Consciousness (C³DoC).
Twelve patients will be randomized to receive placebo for 15 days followed by saxagliptin 5 mg for 15 days (Delayed Start Group), and 12 will receive saxagliptin 5 mg for the full 30 days (Full Treatment Group). Patients will be undercontinuous medical monitoring within C³DoC throughout their approximately 4-week admission. Validated behavioral biomarkers of consciousness (CRS-R) will be collected by blinded certified assessors at baseline (days -7 and 0), day 15, and day 30, with portable EEG-based AI biomarker assessments to corroborate behavioral findings. Follow-up DRS-PI assessments will be conducted at days 60 and 90. A pre-planned adaptive dose escalation design will be employed. The first 8 patients (sentinel cohort) will receive 5 mg (or placebo per delayed start). Upon cohort completion, the independent Safety Monitoring Board (SMB),chaired by a Medical Doctor, will review unblinded safety data. If IRB and FDA IND Exemption approval is obtained for dose escalation, and excellent safety criteria are met (zero SAEs, no Grade 2+ AEs, zero hypoglycemia), the SMB will direct escalation to 10 mg for only the remaining 6 patients in the full treatment arm; All 12 Delayed-Start patients will remain at 5 mg during active treatment (up to 400 mg/day has been shown to be well-tolerated in humans); otherwise, 5 mg continues. Investigators and patients remain blinded throughout. No confirmed adverse events of special interest (AESIs), no permanent study-drug discontinuations for safety reasons, completion of treatment and follow-up through Day 44 before escalation review.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- Model description
- In the present study, we propose to evaluate the safety and preliminary efficacy of saxagliptin in treating prolonged DoC through a randomized, placebo-controlled, double-blind, delayed start Phase IIA trial. Twenty-four (24) patients with prolonged DOC (≥28 days post-injury) will be enrolled at Casa Colina's Center for Disorders of Consciousness (C³DoC). Twelve patients will be randomized to receive placebo for 15 days followed by saxagliptin 5 mg for 15 days (Delayed Start Group), and 12 will receive saxagliptin 5 mg for the full 30 days (Full Treatment Group). Patients will be under continuous medical monitoring within C³DoC throughout their approximately 4-week admission. Validated behavioral biomarkers of consciousness (CRS-R) will be collected by blinded certified assessors at baseline (days -7 and 0), day 15, and day 30, with portable EEG-based AI biomarker assessments to corroborate behavioral findings. Follow-up DRS-PI assessments will be conducted at days 60 and 90.
| Arm | Type | Receives |
|---|---|---|
| Delayed Start Group | Experimental | Drug: Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93)Placebo on days 1-15. Saxagliptin on days 16-30. |
| Full Treatment Group | Experimental | Drug: Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93)Saxagliptin given on days 1-30. |
| Placebo | No intervention | –See delayed group information. Placebo will be given day 0-15 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Any etiology: traumatic brain injury, anoxic brain injury, or vascular (stroke) brain injury.
- Enrolled at Casa Colina Hospital's Center for Disorders of Consciousness (C³DoC).
- Legally authorized representative (LAR) available to provide informed consent.
- Medically stable for participation as determined by the Clinical Co-Investigator (Dr. David Patterson, MD).
Key exclusion criteria (10 listed)
- Type I or Type II Diabetes Mellitus.
- Current use of strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) due to potential saxagliptin exposure increase.
- Current use of insulin or insulin secretagogues.
- Heart failure of NYHA Class II-IV, active decompensated heart failure, or hospitalization for heart failure within 12 months before screening. Because NYHA class is defined by symptoms during physical exertion and cannot be assessed in patients with disorders of consciousness, any patient with a documented diagnosis of heart failure is excluded unless the medical record documents NYHA Class I status before the qualifying brain injury and there has been no subsequent heart failure decompensation or hospitalization.
- Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m², calculated from the screening serum creatinine using the CKD-EPI 2021 equation (Inker et al., 2021). Because reduced muscle mass after prolonged immobility can cause creatinine-based eGFR to overestimate renal function, the Clinical Co-Investigator may additionally obtain a cystatin C-based eGFR; a patient is excluded if either estimate is <60 mL/min/1.73 m².
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 |
|---|---|---|
| Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93)Days 16-30- administer 5 mg/day via G-tube | Drug | Delayed Start Group |
| Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93)Days 1-30- administer 5 mg/day (or 10 mg/day per adaptive design) via G tube | Drug | Full Treatment Group |
Primary outcome
Incidence of serious adverse events (SAEs)
Time frame: From days 1-30
Hypoglycemia (<70 mg/dL via continuous glucose monitoring), non-serious AEs (CTCAE v5.0), and discontinuations vs. placebo (first 15 days), and vitals.
Change in CRS-R total score from baseline to Day 15 (placebo-controlled comparison) and Day 30.
Time frame: Baseline, Days 15 and Days 30
CRS-R assessment divided into 6 subscales Total score ranging from 0-23. Higher scores indicate higher levels of neurological function and consciousness. Higher scores mean a better outcome.
3 secondary outcomes
CRS-R subscales
Time frame: Baseline, day 15, day 30
Portable EEG-based AI biomarker of consciousness level
Time frame: Baseline, days 15, days 30
DRS-PI
Time frame: Days 60 and Days 90
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 5 Nov 2026.
- Background: PubMed 30801440Turner-Stokes L, Dzingina M, Shavelle R, Bill A, Williams H, Sephton K. Estimated Life-Time Savings in the Cost of Ongoing Care Following Specialist Rehabilitation for Severe Traumatic Brain Injury in the United Kingdom. J Head Trauma Rehabil. 2019 Jul/Aug;34(4):205-214. doi: 10.1097/HTR.0000000000000473.
- Background: PubMed 39904872Toker D, Chiang JN, Vespa PM, Schnakers C, Monti MM. The Dipeptidyl Peptidase-4 Inhibitor Saxagliptin as a Candidate Treatment for Disorders of Consciousness: A Deep Learning and Retrospective Clinical Analysis. Neurocrit Care. 2025 Aug;43(1):101-118. doi: 10.1007/s12028-025-02217-0. Epub 2025 Feb 4.
- BackgroundTBI Model systems National Database (2016). Moderate to severe traumatic brain injury is a lifelong condition. https:// www.tbindsc.org/StaticFiles/Documents/CDC_NIDILRR_IAA_Policy.pdf.
- Background: PubMed 28901969Schnakers C, Monti MM. Disorders of consciousness after severe brain injury: therapeutic options. Curr Opin Neurol. 2017 Dec;30(6):573-579. doi: 10.1097/WCO.0000000000000495.
- Background: PubMed 20658796Pistoia F, Mura E, Govoni S, Fini M, Sara M. Awakenings and awareness recovery in disorders of consciousness: is there a role for drugs? CNS Drugs. 2010 Aug;24(8):625-38. doi: 10.2165/11535940-000000000-00000.
- Background: PubMed 33099022Paul D, Sanap G, Shenoy S, Kalyane D, Kalia K, Tekade RK. Artificial intelligence in drug discovery and development. Drug Discov Today. 2021 Jan;26(1):80-93. doi: 10.1016/j.drudis.2020.10.010. Epub 2020 Oct 21.
- Background: PubMed 22123095Pastores SM, Dakwar J, Halpern NA. Costs of critical care medicine. Crit Care Clin. 2012 Jan;28(1):1-10, v. doi: 10.1016/j.ccc.2011.10.003.
- Background: PubMed 22224835Monti MM. Cognition in the vegetative state. Annu Rev Clin Psychol. 2012;8:431-54. doi: 10.1146/annurev-clinpsy-032511-143050. Epub 2012 Jan 3.
- Background: PubMed 11083347Gray DS, Burnham RS. Preliminary outcome analysis of a long-term rehabilitation program for severe acquired brain injury. Arch Phys Med Rehabil. 2000 Nov;81(11):1447-56. doi: 10.1053/apmr.2000.16343.
- Background: PubMed 22725684Gosseries O, Demertzi A, Ledoux D, Bruno MA, Vanhaudenhuyse A, Thibaut A, Laureys S, Schnakers C. Burnout in healthcare workers managing chronic patients with disorders of consciousness. Brain Inj. 2012;26(12):1493-9. doi: 10.3109/02699052.2012.695426. Epub 2012 Jun 22.
- Background: PubMed 15605342Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil. 2004 Dec;85(12):2020-9. doi: 10.1016/j.apmr.2004.02.033.
- Background: PubMed 11839831Giacino JT, Ashwal S, Childs N, Cranford R, Jennett B, Katz DI, Kelly JP, Rosenberg JH, Whyte J, Zafonte RD, Zasler ND. The minimally conscious state: definition and diagnostic criteria. Neurology. 2002 Feb 12;58(3):349-53. doi: 10.1212/wnl.58.3.349.
- Individual participant dataSharing planned: No
Related trials for Vegetative State
Not yet recruiting
Temporal Interference Stimulation for Disorders of Consciousness
Disorder of Consciousness, Minimally Conscious State
Not yet recruiting
AI-Assisted Precision Hyperbaric Oxygen Therapy Based on Dynamic BIS-EEG Feedback for Patients With Disorders of Consciousness
Disorders of Consciousness, Vegetative State
Enrolling by invitation
Prognostication of Recovery in Early Disorders of Consciousness Study
Disorder of Consciousness, Comatose
Not yet recruitingObservational study
Multimodal Assessment and Prognosis in Disorders of Consciousness After Severe Brain Injury (CyDoC-MAP)
Consciousness Disorders, Persistent Vegetative State
Recruiting
Promoting Recovery After Brain Injury Using Focused Ultrasound
Consciousness Disorders, Disorders of Consciousness Due to Severe Brain Injury
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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93) in people with Vegetative State and Minimally Conscious State, run by Casa Colina Hospital and Centers for Healthcare.
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 10 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 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Caroline Schnakers, PhD, Schnakers, PhD ((909)596-7733 ext. 3038, CSchnakers@casacolina.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of serious adverse events (SAEs) (time frame: From days 1-30). The study lists 2 primary outcomes in all. 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 NCT07918274, which also lists 18 linked publications.
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 5 Nov 2026.