ATCell™ Expanded Autologous, Adipose-Derived Mesenchymal Stem Cells Deployed Via Intravenous Infusion

NCT04744051 | Unknown Phase 1 FDA Drug

• 2 other identifiers: CRYO_PCS_ADSC_001FDA File No. 019089
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Post-Concussion Syndrome

Keywords

Concussion; Adipose Derived Stem Cell; Mesenchymal Stem Cell; Adult Stem Cell; Traumatic Brain Injury; Athletes; Military; Chronic Concussion Syndrome; Post Concussion Syndrome

Outcome Measures

Primary Outcomes (12)

• 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.

  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.

  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)

  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

  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

  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.

  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).

  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.

  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.

  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.

  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.

  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.

  Baseline, 1 month post treatment and 6 months post treatment

Study Arms (4)

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.

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.

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.

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.

Drug: Placebo Infusion

Interventions

50 Adipose Derived Stem Cell Infusion DRUG

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.

Also known as: Autologous Adipose Derived Mesenchymal Stem Cells, ADSC Infusion Therapy 50

50 million cell infusion

150 Adipose Derived Stem Cell Infusion DRUG

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.

Also known as: Autologous Adipose Derived Mesenchymal Stem Cells, ADSC Infusion Therapy 150

150 million cell infusion

300 Adipose Derived Stem Cell Infusion DRUG

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.

Also known as: Autologous Adipose Derived Mesenchymal Stem Cells, ADSC Infusion Therapy 300

300 million cell infusion

Placebo Infusion DRUG

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.

Also known as: ADSC Infusion Therapy Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• A. Persistent headaches
• B. Persistent dizziness
• C. Persistent fatigue
• D. Irritability, intolerance to stress, or unusual emotional reactions
• E. Lowered tolerance to noise and/or light
• F. Impaired memory or concentration
• G. 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):
• i) Have undergone a documented hysterectomy and/or bilateral oophorectomy
• ii) Have medically confirmed ovarian failure
• iii) 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

You may not qualify if:

• 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:
• A. Ischemic cardiac disease (eq. unstable angina, myocardial infarction) in the 6 months prior to screening.
• B. 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.
• C. Resting tachycardia (heart rate ≥ 120) or resting bradycardia (heart ≤ 45) on ECG at screening.
• D. Any other cardiovascular illness that in the opinion of the Investigator would render an individual unable to participate in the study.
• E. Individuals with history of heart block.
• F. Individuals with a history of Atrial Fibrillation
• G. 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

Sponsors & Collaborators

• American CryoStem Corporation: lead

Study Sites (1)

BioSolutions Clinical Research Center

La Mesa, California, 91942, United States

Location

Related Publications (6)

• 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.

  PMID: 26905672 BACKGROUND

• Sterr 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.

  PMID: 16460567 BACKGROUND

• Ramos-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.

  PMID: 29396300 BACKGROUND

• McKee 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.

  PMID: 24924675 BACKGROUND

• Thompson 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.

  PMID: 31989101 BACKGROUND

• Toyserkani 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.

  PMID: 28722289 BACKGROUND

MeSH Terms

Conditions

Post-Concussion Syndrome; Brain Concussion; Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Head Injuries, Closed; Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases; Wounds and Injuries; Wounds, Nonpenetrating; Brain Injuries; Brain Diseases; Central Nervous System Diseases

Study Officials

• Peter B Hanson, MD

  Biosolutions Clinical Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Upon receipt of the harvested tissue sample at the processing facility, eligible participants will be randomized in a one in four ratio to either the 50 million, 150 million or 300 million Adipose derives mesenchymal stem cell (ADMSC) dosage or Placebo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: February 8, 2021
• Study Start: February 1, 2021
• Primary Completion: September 30, 2023
• Study Completion: January 31, 2024
• Last Updated: June 9, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)