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Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells

11 juli 2016 bijgewerkt door: Charles Cox, The University of Texas Health Science Center, Houston

The purpose of this study is to determine if bone marrow harvest, BMMNC separation, and re-infusion in adults with acute severe TBI is safe and will improve functional outcome.

12/09/2015 Update: The study is closed to new enrollment and all follow-up visits have been completed. Data analysis is underway.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

Traumatic brain injury (TBI) contributes to 50% of all trauma deaths. The mortality rate for adults following severe TBI (Glasgow Coma Scale < 9) is estimated to be 33%. There is currently no therapy to reverse the primary injury associated with TBI. Over the past 10 years there has been a growing body of literature supporting the use of various progenitor cell types to treat acute neurological injuries such as TBI and stroke. Neural stem cells (adult and embryonic), mesenchymal stromal and multipotent adult progenitor cells, and bone marrow mononuclear cells (from which MSC and MAPCs are derived) have all shown efficacy in pre-clinical models of TBI/stroke through various mechanisms; however, few groups believe that true neural replacement and integration are the putative mechanisms involved in the observed efficacy. More likely is that the progenitor cell populations are modifying the regional response to injury (inflammatory/reparative vs. regenerative), resulting in improved functional outcomes. Our primary hypothesis is that bone marrow mononuclear cell (BMMNC) autologous transplantation after TBI is safe (harvest and infusion related toxicity) after TBI. Our secondary hypothesis is that functional outcomes measures will improve after BMMNC infusion, (3) BMMNC infusion will reduce BBB permeability, (4) BMMNC is neuroprotective and preserves grey matter and white matter volumes after TBI.

Patients, ages18 to 55 years old, admitted to Memorial Hermann Hospital Trauma Center with Glasgow Coma Scores (GCS) of 5 to 8 will be screened. Those patients meeting inclusion/exclusion criteria (or their Legal Authorized Representative [LAR]) will be offered consent to participate. This is a dose-escalation study consisting of 4 cohorts including a control group (5 subjects/cohort). The first five subjects will not undergo the bone marrow harvest procedure; though they will be followed and treated the same as the other study participants and complete all follow-up procedures. Subjects 6-10 will receive the lowest dose target of 6X106 mononuclear cells/kilogram body weight. Subjects 11-15 will receive 9x106 mononuclear cells/kilogram body weight, and lastly Subjects 16-20 will receive 12X106 mononuclear cells/kilogram body weight. The study is NOT powered to detect functional measures of efficacy. However, estimates can be made regarding potential treatment effect sizes to allow rational power analyses for the follow-on Phase II study. This study should determine if bone marrow harvest, BMMNC separation, and reinfusion is safe in adults with acute, severe TBI.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

25

Fase

  • Fase 2
  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Texas
      • Houston, Texas, Verenigde Staten, 77030
        • The University of Texas Health Science Center at Houston

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 55 jaar (Volwassen)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  • Between 18 and 55 years of age on the day of injury;
  • Hospital admission Glasgow Coma Score between 5 and 8;
  • Initial injury occurring less than 24 hours prior to consent;
  • Ability to speak English.

Exclusion Criteria:

  • Known history of:

    1. brain injury,
    2. psychiatric disorder,
    3. neurological impairment and/or deficit
    4. seizure disorder requiring anti-convulsant therapy
    5. recently treated infection
    6. renal disease or altered renal function
    7. hepatic disease or altered liver function
    8. cancer
    9. substance abuse of positive urine drug screen at admission
    10. immunosuppression
    11. HIV
  • Obliteration of perimesencephalic cistern on initial head CT suggesting prolonged hypoxic ischemic insult
  • Initial hospital ICP > 40mm Hg
  • Hemodynamic instability at the time of consent defined as ongoing fluid resuscitation and/or requirement for inotropic support to maintain MAP at or above normals for age - does not include CPP based inotropic support
  • Uncorrected coagulopathy at the time of bone marrow harvest defined as INR >1.6, PTT >36 sec, PLT < 100,000, Fibrinogen < 100g/dL
  • Unstable pelvic fractures defined as requiring operative fixation to manage
  • Pulmonary contusions defined as a chest x-ray with non-anatomic opacification and/or PaO2:FIO2 ratio < 250 associated with the mechanism or injury
  • Greater than AAST Grade I solid or hollow visceral injury of the abdomen and/or pelvis as diagnosed by CT or other imaging
  • Spinal cord injury as diagnosed by CT or MR imaging or clinical findings
  • Persistent hypoxia defined as SaO2 < 94% for > 30 minutes occurring at any time from hospital admission to time of consent
  • Weight > 300 lbs
  • Any contraindication to MRI (including being too large to fit into the MRI)
  • Positive urine pregnancy test
  • Participation in a concurrent intervention study
  • Unwillingness to return for follow-up visits

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: bone marrow mononuclear cells
a bone marrow harvest will be performed within 36 hours of injury followed by a single intravenous infusion of autologous bone marrow mononuclear cells (BMMNCs)
Biologisch: autologous bone marrow mononuclear cells
bone marrow harvest (5ml/kg of body weight) performed within 36 hours of injury, followed by single intravenous infusion of bone marrow mononuclear cells.
Andere namen:
  • BMMNC's

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
neurological events (seizures, changes in Glasgow coma score [GCS], cerebral vascular accident [CVA})
Tijdsspanne: 12 hours post product infusion up to 21 days post infusion
12 hours post product infusion up to 21 days post infusion

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
infectious morbidity
Tijdsspanne: up to 21 days post infusion
up to 21 days post infusion
global functional status per the GOS-E
Tijdsspanne: up to 6 months post injury/treatment
the Glasgow Outcome Scale-Extended (GOS-E) will be administered to assess global functional status (consciousness, independence, work status, return of lifestyle)
up to 6 months post injury/treatment
global functioning per the Disability Rating Scale
Tijdsspanne: up to 6 months post injury/treatment
the Disability Rating Scale (DRS) will be administered which measures level of arousal, cognitive ability related to activities of daily living, motor response, feeding, toileting, grooming and employability
up to 6 months post injury/treatment

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

The University of Texas Health Science Center, Houston

Onderzoekers

  • Hoofdonderzoeker: Charles S Cox, Jr., M.D., The University of Texas Health Science Center, Houston

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 maart 2012

Primaire voltooiing (Werkelijk)

1 mei 2015

Studie voltooiing (Werkelijk)

1 mei 2015

Studieregistratiedata

Eerst ingediend

6 april 2012

Eerst ingediend dat voldeed aan de QC-criteria

9 april 2012

Eerst geplaatst (Schatting)

11 april 2012

Updates van studierecords

Laatste update geplaatst (Schatting)

13 juli 2016

Laatste update ingediend die voldeed aan QC-criteria

11 juli 2016

Laatst geverifieerd

1 juli 2016

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • HSC-MS-11-0477
  • Award No. W81XWH-11-1-0460 (Andere identificatie: USAMRMC)

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