Clinical trial NCT02065245: AllogeneiC Human Mesenchymal Stem Cells (hMSC) in Patients With Aging FRAilTy Via IntravenoUS Delivery
Official title: A Phase I/II, Randomized, Blinded and Placebo-controlled Trial to Evaluate the Safety and Potential Efficacy of Allogeneic Human Mesenchymal Stem Cell Infusion in Patients With Aging Frailty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Frailty
Keywords: Aging Frailty
Frailty
Cardiovascular
Stem Cells
Lead sponsor: Longeveron Inc.
Sponsor class: INDUSTRY
Collaborators: name: The Emmes Company, LLC
First posted: 2014-02-17
Enrollment: 65
Sex: ALL
Minimum age (years): 60
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to look at the safety of treatment with stem cells in patients with Frailty.


Eligibility criteria: Inclusion Criteria:

* Provide written informed consent.
* Subjects age greater than or equal to 60 and less than or equal to 95 years at the time of signing the Informed Consent Form.
* Show signs of frailty apart from a concomitant condition as assessed by the Investigator with a frailty score of 4 to 7 using the Clinical Frailty Scale
* Female subjects with an Follicle-stimulating hormone (FSH) equal to or \> 25.8 milli-international units (mIU) /mL (milliliter), if not currently on hormone replacement therapy.

Exclusion Criteria:

* Score of less than or equal to 24 on the Mini Mental State Examination (MMSE)
* Inability to perform any of the assessments required for endpoint analysis (report safety or tolerability concerns, perform pulmonary function tests, undergo blood draws, read and respond to questionnaires.
* Active listing (or expected future listing) for transplant of any organ.
* Clinically important abnormal screening laboratory values, including but not limited to: hemoglobin \<8 g/dl, white blood cell count \<3000/mm3, platelets\<80,000/mm3, international normalized ratio (INR) \> 1.5 not due to a reversible cause (i.e. Coumadin), aspartate transaminase, alanine transaminase, or alkaline phosphatase \> 3 times upper limit of normal, total bilirubin \> 1.5 mg/dl.
* Serious comorbid illness that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study. Including, but not limited to: HIV, advanced liver or renal failure, class III/IV congestive heart failure, myocardial infarction, unstable angina, or cardiac revascularization within the last six months, or severe obstructive ventilatory defect.
* Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study.
* Be an organ transplant recipient.
* Have a clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma if recurrence occurs.
* Have a non-pulmonary condition that limits lifespan to \< 1 year.
* Have a history of drug or alcohol abuse within the past 24 months.
* Be serum positive for HIV, hepatitis B Surface Antigen (BsAg) or Viremic hepatitis C.
* Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.
* Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female patients must undergo a blood or urine pregnancy test at screening and within 36 hours prior to infusion.
* Have hypersensitivity to dimethyl sulfoxide (DMSO)

Primary outcomes:
measure: Incidence of Any Treatment Emergent - Serious Adverse Events (TE-SAEs)
timeFrame: One Month post infusion
Secondary outcomes:
measure: Change in Frailty as Assessed by CHAMPS Questionnaire
timeFrame: At baseline and 6 month follow-up visit.
measure: Change in Slowing of Mobility as Measured by 4 Meter Gait Speed Test
timeFrame: At baseline and 6 month follow-up visit.
measure: Change in Slowing of Mobility as Measured by SPPB
timeFrame: At baseline and 6 month follow-up visit.
measure: Change in Weight
timeFrame: At baseline and 6 month follow-up visit.
measure: Change in Diminished Hand Grip Strength
timeFrame: At baseline and 6 month follow-up visit.
measure: Change in Exhaustion as Measured by the MFI Questionnaire
timeFrame: At baseline and 6 month follow-up visit.
measure: Change in Quality of Life (QoL) as Measured by the ICECAP Questionnaire
timeFrame: At baseline and 6 month follow-up visit.
measure: Change in Quality of Life (QoL) as Measured by the SF-36 Questionnaire
timeFrame: At baseline and 6 month follow-up visit.
measure: Change in Quality of Life (QoL) as Measured by the EQ-5D-3L Questionnaire
timeFrame: At baseline and 6 month follow-up visit.
measure: Change in Quality of Life (QoL) as Measured by the EQ-5D-3L Overall Health Status Scale.
timeFrame: At baseline and 6 month follow-up visit.
measure: Change in Sense of Smell as Measured by UPSIT
timeFrame: At baseline and 6 month follow-up visit.
measure: Death
timeFrame: Up to 12 months.
measure: Change in Ejection Fraction (EF)
timeFrame: At baseline and 6 month follow-up visit.
measure: Change in Inflammatory Markers Levels
timeFrame: At baseline and 6 month follow-up visit.
measure: Change in Inflammatory Markers
timeFrame: At baseline and 6 month follow-up visit.
measure: Change in Inflammatory Marker D-dimer Levels
timeFrame: At baseline and 6 month follow-up visit.
Other outcomes:
Locations:
city: Miami
country: United States
facility: ISCI/University of Miami Miller School of Medicine
state: Florida
Study officials:
affiliation: ISCI / University of Miami Miller School of Medicine
name: Joshua M Hare, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Golpanian S, DiFede DL, Pujol MV, Lowery MH, Levis-Dusseau S, Goldstein BJ, Schulman IH, Longsomboon B, Wolf A, Khan A, Heldman AW, Goldschmidt-Clermont PJ, Hare JM. Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty. Oncotarget. 2016 Mar 15;7(11):11899-912. doi: 10.18632/oncotarget.7727.
citation: Tompkins BA, DiFede DL, Khan A, Landin AM, Schulman IH, Pujol MV, Heldman AW, Miki R, Goldschmidt-Clermont PJ, Goldstein BJ, Mushtaq M, Levis-Dusseau S, Byrnes JJ, Lowery M, Natsumeda M, Delgado C, Saltzman R, Vidro-Casiano M, Da Fonseca M, Golpanian S, Premer C, Medina A, Valasaki K, Florea V, Anderson E, El-Khorazaty J, Mendizabal A, Green G, Oliva AA, Hare JM. Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1513-1522. doi: 10.1093/gerona/glx137.
citation: Golpanian S, DiFede DL, Khan A, Schulman IH, Landin AM, Tompkins BA, Heldman AW, Miki R, Goldstein BJ, Mushtaq M, Levis-Dusseau S, Byrnes JJ, Lowery M, Natsumeda M, Delgado C, Saltzman R, Vidro-Casiano M, Pujol MV, Da Fonseca M, Oliva AA Jr, Green G, Premer C, Medina A, Valasaki K, Florea V, Anderson E, El-Khorazaty J, Mendizabal A, Goldschmidt-Clermont PJ, Hare JM. Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty. J Gerontol A Biol Sci Med Sci. 2017 Oct 12;72(11):1505-1512. doi: 10.1093/gerona/glx056.