Restoring Awareness

October 30, 2026 updated by: Casa Colina Hospital and Centers for Healthcare

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

24

Phase

  • Phase 2

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

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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.
  • 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.

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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Delayed Start Group

Placebo on days 1-15. Saxagliptin on days 16-30.
Drug: Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93)

Days 16-30- administer 5 mg/day via G-tube

Drug: 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
Experimental: Full Treatment Group

Saxagliptin given on days 1-30.
Drug: Saxagliptin (Mylan Pharmaceuticals Inc., NDC: 0378-4706-93)

Days 16-30- administer 5 mg/day via G-tube

Drug: 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
No Intervention: Placebo

See delayed group information. Placebo will be given day 0-15

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From days 1-30
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.
Baseline, Days 15 and Days 30

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CRS-R subscales
Time Frame: Baseline, day 15, day 30

≥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.
Baseline, day 15, day 30
Portable EEG-based AI biomarker of consciousness level
Time Frame: Baseline, days 15, days 30

A framework to decode consciousness level
Baseline, days 15, days 30
DRS-PI
Time Frame: Days 60 and Days 90

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.
Days 60 and Days 90

Collaborators and Investigators

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

Sponsor

Casa Colina Hospital and Centers for Healthcare

Collaborators

University of California, Los Angeles

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)

November 15, 2026

Primary Completion (Estimated)

October 30, 2029

Study Completion (Estimated)

October 30, 2030

Study Registration Dates

First Submitted

October 12, 2026

First Submitted That Met QC Criteria

October 30, 2026

First Posted (Actual)

November 5, 2026

Study Record Updates

Last Update Posted (Actual)

November 5, 2026

Last Update Submitted That Met QC Criteria

October 30, 2026

Last Verified

October 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SaxaDOC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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