A Phase 2 interventional study of Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93) and Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93) in Vegetative State and Minimally Conscious State, sponsored by Casa Colina Hospital and Centers for Healthcare. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-05.
Sponsored by Casa Colina Hospital and Centers for Healthcare · Phase 2, Interventional, and Treatment
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.
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.
88 studies on the registry are indexed under Persistent Vegetative State; 20 are open to participants now.
This study's planned enrollment of 24 is below the median of 30 across 55 interventional studies indexed under Persistent Vegetative State.
Browse Persistent Vegetative State studies →Casa Colina Hospital and Centers for Healthcare is the lead sponsor of 15 studies on the registry; 10 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Placebo on days 1-15. Saxagliptin on days 16-30.
Drug: Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93)
Saxagliptin given on days 1-30.
Drug: Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93)
See delayed group information. Placebo will be given day 0-15
Days 16-30- administer 5 mg/day via G-tube
Days 1-30- administer 5 mg/day (or 10 mg/day per adaptive design) via G tube
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.
Time frame: 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.
Time frame: Baseline, Days 15 and Days 30
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.
Time frame: Baseline, day 15, day 30
Portable EEG-based AI biomarker of consciousness level
A framework to decode consciousness level
Time frame: 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.
Time frame: Days 60 and Days 90
No study locations are listed for this record.
Plan to share: No
Start is estimated for Nov 2026; primary completion for Oct 2029, 35 months later.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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Casa Colina Hospital and Centers for Healthcare