Post-Concussion SyndromePhase 1NCT04744051
ATCell™ Expanded Autologous, Adipose-Derived Mesenchymal Stem Cells Deployed Via Intravenous Infusion
A Phase 1 study testing 50 Adipose Derived Stem Cell Infusion, 150 Adipose Derived Stem Cell Infusion and 300 Adipose Derived Stem Cell Infusion in people with Post-Concussion Syndrome, run by American CryoStem Corporation at 1 site in United States.
Trial summary
This is a Phase 1 Clinical Safety Study intended to provide preliminary assessments of the safety, tolerability, and clinical alleviation of symptoms associated with Post Concussion Syndrome (PCS), also known as Chronic Concussive Syndrome (CCS). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Post-Concussion Syndrome
- What is being tested?
- 50 Adipose Derived Stem Cell Infusion, 150 Adipose Derived Stem Cell Infusion and 300 Adipose Derived Stem Cell Infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2021to 31 Jan 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Reviewed and personally signed and dated informed consent document indicating that the participant (or legally acceptable representative) has been informed of and understands all pertinent aspects of the study.
- Confirmed Diagnosis of Chronic Concussive Syndrome/Post-Concussive Syndrome: At least three (3) of the following criteria must be met to confirm diagnosis:
- Persistent headaches
- Persistent dizziness
- Persistent fatigue
- Irritability, intolerance to stress, or unusual emotional reactions
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- Lowered tolerance to noise and/or light
- Impaired memory or concentration
- Insomnia
- Female participants of child bearing potential and at risk of pregnancy during the study must agree to use 2 highly effective methods of contraception throughout the study and for 112 days after the last study visit.
- Female participant who are not of childbearing potential (i.e. must meet at least one (1) of the following criteria):
- Have undergone a documented hysterectomy and/or bilateral oophorectomy
- Have medically confirmed ovarian failure
- Achieved postmenopausal status defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or psychological cause and have a serum follicle stimulating hormone (FSH) level confirming the post menopausal state
- Individuals who are willing and able to comply with lifestyle guidelines, scheduled visits, treatment plan, laboratory tests, and other study procedures through the end of the final study visit
- Individuals Aged 18 to 65 at the time of screening and enrollment.
Who cannot join
- Any cardiac pathologies or conditions which may risk the participant or interfere with the ability to interpret the results. Signs and symptoms of clinically significant cardiac disease including but not limited to:
- Ischemic cardiac disease (eq. unstable angina, myocardial infarction) in the 6 months prior to screening.
- New York Heart Association (NYHA) Class III or IV congestive heart failure or known left ventricular dysfunction with ejection fraction ≤ 35%, cardiomyopathy, myocarditis in the 6 months prior to screening.
- Resting tachycardia (heart rate ≥ 120) or resting bradycardia (heart ≤ 45) on ECG at screening.
- Any other cardiovascular illness that in the opinion of the Investigator would render an individual unable to participate in the study.
- Individuals with history of heart block.
Show all 54Show fewer
- Individuals with a history of Atrial Fibrillation
- Individuals that have had stents implanted within one year of recruitment
- History of transient ischemic attack in the 6 months prior to screening, diagnosis of stroke with residual deficits (eq. aphasia, substantial motor or sensory deficits) diagnosis of stroke with residual deficits (eq. aphasia, substantial motor or sensory deficits) that would preclude completion of required study activities
- Resting, sitting blood pressure (BP) ≥ 160 mm Hg in systolic pressure or ≥ 100 mm Hg in diastolic pressure at screening. If a participant is found to have untreated significant hypertension at screening and antihypertensive treatment is initiated, assessment for study eligibility should be deferred until BP and antihypertensive medication have been stable for at least 1 month. For participants with previously diagnosed hypertension, antihypertensive medications must be stable for at least 1 month prior to screening
- Participants who have evidence of orthostatic hypotension based upon replicate orthostatic blood pressure measurements. If orthostatic blood pressure change is not able to be determined (e.g., unable to establish a stable supine systolic and diastolic blood pressure) the participant is not eligible for the study
- Individuals with a history of Deep Vein Thrombosis (DVT) or pulmonary embolism
- Individuals with a history or family history of thrombophilia such as Factor V Leiden
- Individuals that have had stents implanted within the past year
- Individuals that are currently being treated with an anticoagulant medication
- History, diagnosis, or signs and symptoms of clinically significant neurological disease, including but not limited to:
- Alzheimer's disease or other type of dementia
- Peripheral or autonomic neuropathy
- Multiple sclerosis
- Epilepsy or seizure disorder with history of seizure within the last 2 years
- Myopathy
- White matter disease
- Individuals currently being treated with specific prescription immunomodulatory agents:
- Certolizumab (Cimzia™)
- Infliximab (REMICADE™)
- Etanercept (Enbrel™)
- Prednisone (Deltasone, Rayos, Prednisone Intensol)
- Prednisolone (Omnipred™)
- Dexamethasone (Ozurdex™)
- Any drug which the investigator believes would compromise the results or interfere with ATCell™ effectiveness
- Participant with any active or chronic infection
- Life-threading organ dysfunction
- Planned surgical procedure during the duration of the study
- Largely or wholly incapacitated (eq. individual bedridden or confined to wheelchair, permitting little or no self care)
- Pregnant or actively breastfeeding females; females of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study, meaning 6 months after ATCell™ administration
- Severe physical limitations or disabilities
- Participants who are seropositive for Human Immunodeficiency Virus -1 (HIV1), Human Immunodeficiency Virus -2 (HIV2), Hepatitis B Surface Antigen and Hepatitis C, indicative of current infection
- Participant unable to give written consent in accordance with institutional review board guidelines
- Treatment with any immunosuppressive therapy within 3 months of evaluation
- Current or recent treatment (within 3 months of evaluation) with an investigational drug and/or therapy (phase 1-4) within 90 days of screening
- Individuals with a concurrent diagnosis of malignant neoplasm (cancer)
- History of cancer within 5 years prior to screening, except for cutaneous basal cell or squamous cell cancer resolved by excision
- Individuals with inadequate subcutaneous tissue to allow for appropriate lipoaspirate collection
- Other severe or chronic medical psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make this individual inappropriate for entry into this study
- Individuals with immunodeficiencies or severe autoimmune disease
- Individuals allergic to local anesthetics
- Individuals with any contraindication to liposuction, in the investigator's opinion
- History of coagulation disorders that would put them at risk
- Individuals, in the opinion of the investigator, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason
- The individual is involved in an active civil, criminal or workers compensation case other than the NFL class action
- Individuals unable or unwilling to return for the required follow-up evaluations
- Presence of drugs of abuse (including cannabis and prescription medications without valid prescription), or illegal drugs in the urine toxicology test obtained at screening
- History of known alcohol, analgesic or drug abuse within 2 years of screening
- Individuals who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or who are employees directly involved in the conduct of the study
Trial locations and contacts
1 site in 1 country.
United States1 site
BioSolutions Clinical Research Center
La Mesa, California, 91942
About this study
Official title: ATCell™ Expanded Autologous, Adipose-Derived Mesenchymal Stem Cells Deployed Via Intravenous Infusion for the Treatment of Post Concussion Syndrome (PCS) in Retired Military and Athletes
This is a Phase 1 Clinical Safety Study intended to provide preliminary assessments of the safety, tolerability, and clinical alleviation of symptoms associated with Post Concussion Syndrome (PCS), also known as Chronic Concussive Syndrome (CCS).
Read the detailed description
The proposed study is a single-site, double-blinded, placebo-controlled study involving a single administration of either individual, autologous ATCell™ lines suspended in 5% dextrose lactated Ringer's solution or a vehicle (5% dextrose Lactated Ringer's solution) not containing cells. Each ATCell™ cell line will be created from cells grown from the stromal vascular fraction (SVF) of a participant's own adipose tissue collected by liposuction, and each treated participant will only receive their own cells.
Within the treated group, 3 dosing levels will be explored: 50 million cells, 150 million cells, or 300 million cells, and a Placebo group which will receive 5% dextrose lactated Ringer's solution free of cells. Participant follow-ups will take place 1 day following the tissue harvest procedure and, 1 day, 1 week, 1 month, 3 months, and 6 months following ATCell™ treatment. Comprehensive participant's evaluations involving data collection will take place 1, 3, and 6 months following treatment.
It has been proposed that in general, mild traumatic brain injuries (TBI) events need to be taken far more seriously, and that even mild TBI events can result in lasting negative consequences as evidenced by lower performances on neuropsychological assessments when compared with age-matched controls2. In fact, this condition may eventually lead to Alzheimer's Disease (AD) as well as Chronic Traumatic Encephalopathy (CTE), which, together may be termed the AD-like dementias3, further underscoring the need for effective clinical intervention. Currently, no effective treatments are available for this condition aside from treatment of the symptoms, although some more comprehensive treatments have been proposed.
- Conditions
- Post-Concussion Syndrome
- Being tested
- 50 Adipose Derived Stem Cell Infusion, 150 Adipose Derived Stem Cell Infusion, 300 Adipose Derived Stem Cell Infusion, Placebo Infusion
- Keywords
- Concussion, Adipose Derived Stem Cell, Mesenchymal Stem Cell, Adult Stem Cell, Traumatic Brain Injury, Athletes, Military, Chronic Concussion Syndrome, Post Concussion Syndrome
- Medical subject headings
- Post-Concussion Syndrome, Brain Concussion, Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
50 Adipose Derived Stem Cell InfusionDrug
Also called Autologous Adipose Derived Mesenchymal Stem Cells, ADSC Infusion Therapy 50
Each participant in this arm will receive a single dose of 50 million cultured adipose derived stem cells derived from their own adipose (fat) tissue via infusion therapy delivery over the course of one hour.
150 Adipose Derived Stem Cell InfusionDrug
Also called Autologous Adipose Derived Mesenchymal Stem Cells, ADSC Infusion Therapy 150
Each participant in this arm will receive a single dose of 150 million cultured adipose derived stem cells derived from their own adipose (fat) tissue via infusion therapy delivery over the course of one hour.
300 Adipose Derived Stem Cell InfusionDrug
Also called Autologous Adipose Derived Mesenchymal Stem Cells, ADSC Infusion Therapy 300
Each participant in this arm will receive a single dose of 300 million cultured adipose derived stem cells derived from their own adipose (fat) tissue via infusion therapy delivery over the course of one hour.
Placebo InfusionDrug
Also called ADSC Infusion Therapy Placebo
Each participant in this arm will receive a single dose of placebo. Upon completion of the study each placebo participant will with be given the option to be treated with their cultured adipose derived stem cells derived from their own adipose (fat) tissue via infusion therapy delivery over the course of one hour. Dosage for the crossover will be determined by the PI following review of data collected from the other arms of the study.
| Study group | Role | What they receive |
|---|---|---|
| 50 million cell infusion | Active comparator | Each participant in this arm will receive a single dose of 50 million cultured adipose derived stem cells derived from their own adipose (fat) tissue via infusion therapy delivery over the course of one hour. Receives: Drug: 50 Adipose Derived Stem Cell Infusion |
| 150 million cell infusion | Active comparator | Each participant in this arm will receive a single dose of 150 million cultured adipose derived stem cells derived from their own adipose (fat) tissue via infusion therapy delivery over the course of one hour. Receives: Drug: 150 Adipose Derived Stem Cell Infusion |
| 300 million cell infusion | Active comparator | Each participant in this arm will receive a single dose of 300 million cultured adipose derived stem cells derived from their own adipose (fat) tissue via infusion therapy delivery over the course of one hour. Receives: Drug: 300 Adipose Derived Stem Cell Infusion |
| Placebo | Placebo comparator | Each participant in this arm will receive a single dose of placebo. Upon completion of the study each placebo participant with be given the option to be treated with their cultured adipose derived stem cells derived from their own adipose (fat) tissue via infusion therapy delivery over the course of one hour. Dosage for the crossover will be determined by the PI following review of data collected from the other arms of the study. Receives: Drug: Placebo Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Health Status using the 36 item Short Form Health Survey (SF-36)
Completed by Participant as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores of completed SF-36 will be numerically determined and compared to baseline. Changes against baseline will be represented numerically (positive or negative).The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.
Measured: Baseline, 1 month and 6 months post treatment
Assessment of Visual Attention and Task Switching
Administered by study staff as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores How long it takes the participant to connect a sequence of 25 consecutive targets in sequential order on a sheet of paper or computer screen to complete the two tests will be numerically determined (seconds) and compared to baseline. The goal of the test is for the subject to finish both parts as quickly as possible, with the time taken to complete the test being used as the primary performance metric If a person makes an error in the test, there's no change in the score other than that it makes their completion time longer since the person has to go back to correct the error, thus extending their time, shorter completion times indicate improved scores.
Measured: Baseline, 1 month and 6 months post treatment
Assessment of Contextual Verbal Learning
Administered by study staff as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores will be numerically determined and compared to baseline. Changes against baseline will be represented numerically (positive or negative)
Measured: Baseline, 1 month post treatment and 6 months post treatment
Assessment of Verbal Fluency
Administered by study staff as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores will be numerically determined and compared to baseline. Changes against baseline will be represented numerically (positive or negative). Scoring is based on total word numbers (expressed in 60 seconds), higher totals in tests indicate improvement
Measured: Baseline, 1 month post treatment and 6 months post treatment
Assessment of Attention and Executive functions
Administered by study staff as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores will be numerically determined as the number of correct answers provided in 90 seconds. and compared to baseline. Changes against baseline will be represented numerically (positive or negative). AN increase in total correct answers will indicate improvement
Measured: Baseline, 1 month post treatment and 6 months post treatment
Assessment of Unstructured Verbal Learning and Memory
Administered by study staff as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores will be numerically determined based the total number of correct answers in 3 categories of 12 and compared to baseline as a percentage. Changes against baseline will be represented numerically (positive or negative), Improved scores will indicate improvement.
Measured: Baseline, 1 month post treatment and 6 months post treatment
Assessment of Visuospatial Learning and Memory
Administered by study staff as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores will be numerically determined (percent) based upon correct recall and compared to baseline. Changes against baseline will be represented numerically (positive or negative).
Measured: Baseline, 1 month post treatment and 6 months post treatment
Assessment of Symptoms of Anxiety over Time
Completed by Participant as a part of physician visits at baseline, and 1, and 6 months following treatment. Each question is scored on a scale of 1 to 4 for 22 questions, total score is the sum of the score of each item (1-4) will be numerically determined and compared to baseline. Changes against baseline will be represented numerically (positive or negative). Lower scores will indicate improvement.
Measured: Baseline, 1 month post treatment and 6 months post treatment
Assessment of Pain
Completed by Participant as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores will be numerically determined on a scale of 1 to 10 and compared to baseline. Changes against baseline will be represented numerically (positive or negative) lower scores will indicate improvement.
Measured: Baseline, 1 month post treatment and 6 months post treatment
Assessment of Sleep Quality
Completed by Participant as a part of physician visits at baseline, and 1, and 6 months following treatment. Scores will be numerically determined (1 to 3) for 7 questions (maximum score of 21) and compared to baseline. Changes against baseline will be represented numerically (positive or negative). Lower total scores indicate improvement.
Measured: Baseline, 1 month post treatment and 6 months post treatment
Assessment of Treatment by Participant
Completed by Participant as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores will be numerically determined on a 1 to 7 basis, and compared to baseline. Changes against baseline will be represented numerically (positive or negative) lower scores represent improvement.
Measured: Baseline, 1 month post treatment and 6 months post treatment
Assessment of Depression by Participant
Completed by Participant as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores will be numerically determined (1 to3) for 9 questions (maximum score of 27) and compared to baseline. Changes against baseline will be represented numerically (positive or negative), lower scores indicate improvement.
Measured: Baseline, 1 month post treatment and 6 months post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2021
- Study start1 Feb 2021
- Primary completion30 Sep 2023 (estimated)
- Study completion31 Jan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Post-Concussion SyndromeStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The proposed study is a single-site, double-blinded, placebo-controlled study involving a single administration of either individual, autologous ATCell™ lines suspended in 5% dextrose lactated Ringer's solution or a vehicle (5% dextrose lactated Ringer's solution) not containing cells. Each ATCell™ cell line will be created from cells grown from the stromal vascular fraction (SVF) of a participant's own adipose tissue collected by liposuction, and each treated participant will only receive their own cells.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- American CryoStem Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Peter B Hanson, MD, Principal investigator, Biosolutions Clinical Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04744051
- Sponsor's protocol ID
- CRYO_PCS_ADSC_001
- Other IDs
- FDA File No. 019089
- Status last verified
- Jun 2023
- First submitted
- 15 Dec 2020
- Last updated
- 9 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Stein MB, Ursano RJ, Campbell-Sills L, Colpe LJ, Fullerton CS, Heeringa SG, Nock MK, Sampson NA, Schoenbaum M, Sun X, Jain S, Kessler RC. Prognostic Indicators of Persistent Post-Concussive Symptoms after Deployment-Related Mild Traumatic Brain Injury: A Prospective Longitudinal Study in U.S. Army Soldiers. J Neurotrauma. 2016 Dec 1;33(23):2125-2132. doi: 10.1089/neu.2015.4320. Epub 2016 Apr 8.
PubMed 26905672Sterr A, Herron KA, Hayward C, Montaldi D. Are mild head injuries as mild as we think? Neurobehavioral concomitants of chronic post-concussion syndrome. BMC Neurol. 2006 Feb 6;6:7. doi: 10.1186/1471-2377-6-7.
PubMed 16460567Ramos-Cejudo J, Wisniewski T, Marmar C, Zetterberg H, Blennow K, de Leon MJ, Fossati S. Traumatic Brain Injury and Alzheimer's Disease: The Cerebrovascular Link. EBioMedicine. 2018 Feb;28:21-30. doi: 10.1016/j.ebiom.2018.01.021. Epub 2018 Jan 31.
PubMed 29396300McKee AC, Robinson ME. Military-related traumatic brain injury and neurodegeneration. Alzheimers Dement. 2014 Jun;10(3 Suppl):S242-53. doi: 10.1016/j.jalz.2014.04.003.
PubMed 24924675Thompson M, Mei SHJ, Wolfe D, Champagne J, Fergusson D, Stewart DJ, Sullivan KJ, Doxtator E, Lalu M, English SW, Granton J, Hutton B, Marshall J, Maybee A, Walley KR, Santos CD, Winston B, McIntyre L. Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: An updated systematic review and meta-analysis. EClinicalMedicine. 2020 Jan 17;19:100249. doi: 10.1016/j.eclinm.2019.100249. eCollection 2020 Feb.
PubMed 31989101Toyserkani NM, Jorgensen MG, Tabatabaeifar S, Jensen CH, Sheikh SP, Sorensen JA. Concise Review: A Safety Assessment of Adipose-Derived Cell Therapy in Clinical Trials: A Systematic Review of Reported Adverse Events. Stem Cells Transl Med. 2017 Sep;6(9):1786-1794. doi: 10.1002/sctm.17-0031. Epub 2017 Jul 19.
PubMed 28722289
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ATCell™ Expanded Autologous, Adipose-Derived Mesenchymal Stem Cells Deployed Via Intravenous Infusion for the Treatment of Post Concussion Syndrome (PCS) in Retired Military and Athletes
- ClinicalTrials.gov ID
- NCT04744051
- Acronym / sponsor ID
- CRYO_PCS_ADSC_001
- Conditions
- Post-Concussion Syndrome
- Keywords
- Concussion, Adipose Derived Stem Cell, Mesenchymal Stem Cell, Adult Stem Cell, Traumatic Brain Injury, Athletes, Military, Chronic Concussion Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- American CryoStem CorporationIndustry (pharma, biotech, devices)
- Study start
- 1 Feb 2021 (actual)
- Primary completion
- 30 Sep 2023 (estimated)
- Study completion
- 31 Jan 2024 (estimated)
- First posted
- 8 Feb 2021 (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.
This is a Phase 1 Clinical Safety Study intended to provide preliminary assessments of the safety, tolerability, and clinical alleviation of symptoms associated with Post Concussion Syndrome (PCS), also known as Chronic Concussive Syndrome (CCS).
Detailed description
The proposed study is a single-site, double-blinded, placebo-controlled study involving a single administration of either individual, autologous ATCell™ lines suspended in 5% dextrose lactated Ringer's solution or a vehicle (5% dextrose Lactated Ringer's solution) not containing cells. Each ATCell™ cell line will be created from cells grown from the stromal vascular fraction (SVF) of a participant's own adipose tissue collected by liposuction, and each treated participant will only receive their own cells.
Within the treated group, 3 dosing levels will be explored: 50 million cells, 150 million cells, or 300 million cells, and a Placebo group which will receive 5% dextrose lactated Ringer's solution free of cells. Participant follow-ups will take place 1 day following the tissue harvest procedure and, 1 day, 1 week, 1 month, 3 months, and 6 months following ATCell™ treatment. Comprehensive participant's evaluations involving data collection will take place 1, 3, and 6 months following treatment.
It has been proposed that in general, mild traumatic brain injuries (TBI) events need to be taken far more seriously, and that even mild TBI events can result in lasting negative consequences as evidenced by lower performances on neuropsychological assessments when compared with age-matched controls2. In fact, this condition may eventually lead to Alzheimer's Disease (AD) as well as Chronic Traumatic Encephalopathy (CTE), which, together may be termed the AD-like dementias3, further underscoring the need for effective clinical intervention. Currently, no effective treatments are available for this condition aside from treatment of the symptoms, although some more comprehensive treatments have been proposed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- The proposed study is a single-site, double-blinded, placebo-controlled study involving a single administration of either individual, autologous ATCell™ lines suspended in 5% dextrose lactated Ringer's solution or a vehicle (5% dextrose lactated Ringer's solution) not containing cells. Each ATCell™ cell line will be created from cells grown from the stromal vascular fraction (SVF) of a participant's own adipose tissue collected by liposuction, and each treated participant will only receive their own cells.
| Arm | Type | Receives |
|---|---|---|
| 50 million cell infusion | Active comparator | Drug: 50 Adipose Derived Stem Cell InfusionEach participant in this arm will receive a single dose of 50 million cultured adipose derived stem cells derived from their own adipose (fat) tissue via infusion therapy delivery over the course of one hour. |
| 150 million cell infusion | Active comparator | Drug: 150 Adipose Derived Stem Cell InfusionEach participant in this arm will receive a single dose of 150 million cultured adipose derived stem cells derived from their own adipose (fat) tissue via infusion therapy delivery over the course of one hour. |
| 300 million cell infusion | Active comparator | Drug: 300 Adipose Derived Stem Cell InfusionEach participant in this arm will receive a single dose of 300 million cultured adipose derived stem cells derived from their own adipose (fat) tissue via infusion therapy delivery over the course of one hour. |
| Placebo | Placebo comparator | Drug: Placebo InfusionEach participant in this arm will receive a single dose of placebo. Upon completion of the study each placebo participant with be given the option to be treated with their cultured adipose derived stem cells derived from their own adipose (fat) tissue via infusion therapy delivery over the course of one hour. Dosage for the crossover will be determined by the PI following review of data collected from the other arms of the study. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Reviewed and personally signed and dated informed consent document indicating that the participant (or legally acceptable representative) has been informed of and understands all pertinent aspects of the study.
- Confirmed Diagnosis of Chronic Concussive Syndrome/Post-Concussive Syndrome: At least three (3) of the following criteria must be met to confirm diagnosis:
- Female participants of child bearing potential and at risk of pregnancy during the study must agree to use 2 highly effective methods of contraception throughout the study and for 112 days after the last study visit.
- Female participant who are not of childbearing potential (i.e. must meet at least one (1) of the following criteria):
- Individuals who are willing and able to comply with lifestyle guidelines, scheduled visits, treatment plan, laboratory tests, and other study procedures through the end of the final study visit
Key exclusion criteria (54 listed)
- Any cardiac pathologies or conditions which may risk the participant or interfere with the ability to interpret the results. Signs and symptoms of clinically significant cardiac disease including but not limited to:
- History of transient ischemic attack in the 6 months prior to screening, diagnosis of stroke with residual deficits (eq. aphasia, substantial motor or sensory deficits) diagnosis of stroke with residual deficits (eq. aphasia, substantial motor or sensory deficits) that would preclude completion of required study activities
- Resting, sitting blood pressure (BP) ≥ 160 mm Hg in systolic pressure or ≥ 100 mm Hg in diastolic pressure at screening. If a participant is found to have untreated significant hypertension at screening and antihypertensive treatment is initiated, assessment for study eligibility should be deferred until BP and antihypertensive medication have been stable for at least 1 month. For participants with previously diagnosed hypertension, antihypertensive medications must be stable for at least 1 month prior to screening
- Participants who have evidence of orthostatic hypotension based upon replicate orthostatic blood pressure measurements. If orthostatic blood pressure change is not able to be determined (e.g., unable to establish a stable supine systolic and diastolic blood pressure) the participant is not eligible for the study
- Individuals with a history of Deep Vein Thrombosis (DVT) or pulmonary embolism
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 |
|---|---|---|
| 50 Adipose Derived Stem Cell InfusionAlso: Autologous Adipose Derived Mesenchymal Stem Cells, ADSC Infusion Therapy 50Each participant in this arm will receive a single dose of 50 million cultured adipose derived stem cells derived from their own adipose (fat) tissue via infusion therapy delivery over the course of one hour. | Drug | 50 million cell infusion |
| 150 Adipose Derived Stem Cell InfusionAlso: Autologous Adipose Derived Mesenchymal Stem Cells, ADSC Infusion Therapy 150Each participant in this arm will receive a single dose of 150 million cultured adipose derived stem cells derived from their own adipose (fat) tissue via infusion therapy delivery over the course of one hour. | Drug | 150 million cell infusion |
| 300 Adipose Derived Stem Cell InfusionAlso: Autologous Adipose Derived Mesenchymal Stem Cells, ADSC Infusion Therapy 300Each participant in this arm will receive a single dose of 300 million cultured adipose derived stem cells derived from their own adipose (fat) tissue via infusion therapy delivery over the course of one hour. | Drug | 300 million cell infusion |
| Placebo InfusionAlso: ADSC Infusion Therapy PlaceboEach participant in this arm will receive a single dose of placebo. Upon completion of the study each placebo participant will with be given the option to be treated with their cultured adipose derived stem cells derived from their own adipose (fat) tissue via infusion therapy delivery over the course of one hour. Dosage for the crossover will be determined by the PI following review of data collected from the other arms of the study. | Drug | Placebo |
Primary outcome
Health Status using the 36 item Short Form Health Survey (SF-36)
Time frame: Baseline, 1 month and 6 months post treatment
Completed by Participant as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores of completed SF-36 will be numerically determined and compared to baseline. Changes against baseline will be represented numerically (positive or negative).The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.
Assessment of Visual Attention and Task Switching
Time frame: Baseline, 1 month and 6 months post treatment
Administered by study staff as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores How long it takes the participant to connect a sequence of 25 consecutive targets in sequential order on a sheet of paper or computer screen to complete the two tests will be numerically determined (seconds) and compared to baseline. The goal of the test is for the subject to finish both parts as quickly as possible, with the time taken to complete the test being used as the primary performance metric If a person makes an error in the test, there's no change in the score other than that it makes their completion time longer since the person has to go back to correct the error, thus extending their time, shorter completion times indicate improved scores.
Assessment of Contextual Verbal Learning
Time frame: Baseline, 1 month post treatment and 6 months post treatment
Administered by study staff as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores will be numerically determined and compared to baseline. Changes against baseline will be represented numerically (positive or negative)
Assessment of Verbal Fluency
Time frame: Baseline, 1 month post treatment and 6 months post treatment
Administered by study staff as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores will be numerically determined and compared to baseline. Changes against baseline will be represented numerically (positive or negative). Scoring is based on total word numbers (expressed in 60 seconds), higher totals in tests indicate improvement
Assessment of Attention and Executive functions
Time frame: Baseline, 1 month post treatment and 6 months post treatment
Administered by study staff as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores will be numerically determined as the number of correct answers provided in 90 seconds. and compared to baseline. Changes against baseline will be represented numerically (positive or negative). AN increase in total correct answers will indicate improvement
Assessment of Unstructured Verbal Learning and Memory
Time frame: Baseline, 1 month post treatment and 6 months post treatment
Administered by study staff as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores will be numerically determined based the total number of correct answers in 3 categories of 12 and compared to baseline as a percentage. Changes against baseline will be represented numerically (positive or negative), Improved scores will indicate improvement.
Assessment of Visuospatial Learning and Memory
Time frame: Baseline, 1 month post treatment and 6 months post treatment
Administered by study staff as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores will be numerically determined (percent) based upon correct recall and compared to baseline. Changes against baseline will be represented numerically (positive or negative).
Assessment of Symptoms of Anxiety over Time
Time frame: Baseline, 1 month post treatment and 6 months post treatment
Completed by Participant as a part of physician visits at baseline, and 1, and 6 months following treatment. Each question is scored on a scale of 1 to 4 for 22 questions, total score is the sum of the score of each item (1-4) will be numerically determined and compared to baseline. Changes against baseline will be represented numerically (positive or negative). Lower scores will indicate improvement.
Assessment of Pain
Time frame: Baseline, 1 month post treatment and 6 months post treatment
Completed by Participant as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores will be numerically determined on a scale of 1 to 10 and compared to baseline. Changes against baseline will be represented numerically (positive or negative) lower scores will indicate improvement.
Assessment of Sleep Quality
Time frame: Baseline, 1 month post treatment and 6 months post treatment
Completed by Participant as a part of physician visits at baseline, and 1, and 6 months following treatment. Scores will be numerically determined (1 to 3) for 7 questions (maximum score of 21) and compared to baseline. Changes against baseline will be represented numerically (positive or negative). Lower total scores indicate improvement.
Assessment of Treatment by Participant
Time frame: Baseline, 1 month post treatment and 6 months post treatment
Completed by Participant as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores will be numerically determined on a 1 to 7 basis, and compared to baseline. Changes against baseline will be represented numerically (positive or negative) lower scores represent improvement.
Assessment of Depression by Participant
Time frame: Baseline, 1 month post treatment and 6 months post treatment
Completed by Participant as a part of physician visits at baseline, and 1, and 6 months following treatment . Scores will be numerically determined (1 to3) for 9 questions (maximum score of 27) and compared to baseline. Changes against baseline will be represented numerically (positive or negative), lower scores indicate improvement.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2023.
- Background: PubMed 26905672Stein MB, Ursano RJ, Campbell-Sills L, Colpe LJ, Fullerton CS, Heeringa SG, Nock MK, Sampson NA, Schoenbaum M, Sun X, Jain S, Kessler RC. Prognostic Indicators of Persistent Post-Concussive Symptoms after Deployment-Related Mild Traumatic Brain Injury: A Prospective Longitudinal Study in U.S. Army Soldiers. J Neurotrauma. 2016 Dec 1;33(23):2125-2132. doi: 10.1089/neu.2015.4320. Epub 2016 Apr 8.
- Background: PubMed 16460567Sterr A, Herron KA, Hayward C, Montaldi D. Are mild head injuries as mild as we think? Neurobehavioral concomitants of chronic post-concussion syndrome. BMC Neurol. 2006 Feb 6;6:7. doi: 10.1186/1471-2377-6-7.
- Background: PubMed 29396300Ramos-Cejudo J, Wisniewski T, Marmar C, Zetterberg H, Blennow K, de Leon MJ, Fossati S. Traumatic Brain Injury and Alzheimer's Disease: The Cerebrovascular Link. EBioMedicine. 2018 Feb;28:21-30. doi: 10.1016/j.ebiom.2018.01.021. Epub 2018 Jan 31.
- Background: PubMed 24924675McKee AC, Robinson ME. Military-related traumatic brain injury and neurodegeneration. Alzheimers Dement. 2014 Jun;10(3 Suppl):S242-53. doi: 10.1016/j.jalz.2014.04.003.
- Background: PubMed 31989101Thompson M, Mei SHJ, Wolfe D, Champagne J, Fergusson D, Stewart DJ, Sullivan KJ, Doxtator E, Lalu M, English SW, Granton J, Hutton B, Marshall J, Maybee A, Walley KR, Santos CD, Winston B, McIntyre L. Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: An updated systematic review and meta-analysis. EClinicalMedicine. 2020 Jan 17;19:100249. doi: 10.1016/j.eclinm.2019.100249. eCollection 2020 Feb.
- Background: PubMed 28722289Toyserkani NM, Jorgensen MG, Tabatabaeifar S, Jensen CH, Sheikh SP, Sorensen JA. Concise Review: A Safety Assessment of Adipose-Derived Cell Therapy in Clinical Trials: A Systematic Review of Reported Adverse Events. Stem Cells Transl Med. 2017 Sep;6(9):1786-1794. doi: 10.1002/sctm.17-0031. Epub 2017 Jul 19.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Peter B Hanson, MD principal investigator
Biosolutions Clinical Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 50 Adipose Derived Stem Cell Infusion, 150 Adipose Derived Stem Cell Infusion and 300 Adipose Derived Stem Cell Infusion in people with Post-Concussion Syndrome, run by American CryoStem Corporation 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 16 inclusion and 54 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: status not confirmed, as of the sponsor's last update on 9 Jun 2023. 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Health Status using the 36 item Short Form Health Survey (SF-36) (time frame: Baseline, 1 month and 6 months post treatment). The study lists 12 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 NCT04744051, which also lists 6 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 9 Jun 2023.