Clinical trial NCT02795052: Neurologic Stem Cell Treatment Study
Official title: Neurologic Bone Marrow Derived Stem Cell Treatment Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Neurologic Disorders
Nervous System Diseases
Neurodegenerative Diseases
Neurological Disorders
Stroke
Traumatic Brain Injury
Cadasil
Chronic Traumatic Encephalopathy
Cerebral Infarction
Cerebral Ischemia
Cerebral Stroke
Cerebral Hemorrhage
Parkinson
Multi-System Degeneration
MSA - Multiple System Atrophy
Progressive Supranuclear Palsy
ALS
Amyotrophic Lateral Sclerosis
Neuropathy
Diabetic Neuropathies
Alzheimer Disease
Dementia
Frontotemporal Dementia
Lewy Body Disease
Cognitive Impairment
Lewy Body Variant of Alzheimer Disease
Keywords: Neurologic Disease
Cerebral Vascular Accident
Stroke
Traumatic Brain Injury
Multiple Sclerosis
Parkinsons Disease
Neuropathy
Diabetic Neuropathy
Cerebral Ischemia
Cognitive Impairment
Dementia
Neurodegeneration
Lead sponsor: MD Stem Cells
Sponsor class: INDUSTRY
First posted: 2016-06-09
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Intravenous and intranasal bone marrow derived stem cells.
Primary purpose: TREATMENT

Brief summary: This is a human clinical study involving the isolation of autologous bone marrow derived stem cells (BMSC) and transfer to the vascular system and inferior 1/3 of the nasal passages in order to determine if such a treatment will provide improvement in neurologic function for patients with certain neurologic conditions. http://mdstemcells.com/nest/

Detailed description: Various clinical studies have registered with the National Institutes of Health (NIH) to study neurologic diseases and damage. There have also been a number of journal reports of the benefits of treatment with BMSC for diseases and damage to nervous tissue. The investigators hope to add to the volume of literature regarding the use of BMSC in those neurologic diseases and conditions identified as likely to respond to this treatment.

Intravenous administration of BMSC is a well-established approach to neurologic disease and injury with much support for its effectiveness in the pre-clinical and clinical literature. BMSC and the associated bone marrow fraction are posited to have a number of different mechanisms by which they may potentially improve neurologic function. In regards their ability to penetrate the blood-brain barrier for potential neuronal transdifferentiation and direct impact on the neurons and glial tissue within the brain, it should be remembered that within the diencephalon there are specific circumventricular organs which lie in the wall of the third ventricle. These are noteworthy for a significantly diminished blood-brain barrier and glial limitans which facilitates their function of coordinating homeostatic mechanisms of the endocrine and nervous systems. Therefore the investigators believe entry of BMSC may be facilitated in this area of the brain.

The NEST Study provides a treatment Arm 1 which combines intravenous BMSC with topical application of BMSC to the lower 1/3 of the nasal passages as a means of introducing BMSC to the Central Nervous System (CNS). This is applied bilaterally to the inferior nasal conchas and meatuses. The Trigeminal Nerve or 5th Cranial Nerve is a paired, large sensory and motor nerve with multiple branches. It provides sensation to the surface and interior structures of the face including the nasal mucosa that lines the nose. The nerves of the Trigeminal Nerve providing sensation to this area converge and enter the brain at the level of the pons. There is documentation in the scientific literature that intranasal delivery of BMSC allows the BMSC to follow the pathways of the trigeminal nerve, facilitating entry into the parenchyma and cerebral spinal fluid (CSF) for effects on the CNS.

Eligibility criteria: Inclusion Criteria:

1. Have documented functional damage to the central or peripheral nervous system unlikely to improve with present standard of care.
2. Be at least 6 months post-onset of the disease.
3. If under current medical therapy (pharmacologic or surgical treatment) for the condition be considered stable on that treatment and unlikely to have reversal of the associated neurologic functional damage as a result of the ongoing pharmacologic or surgical treatment.
4. In the estimation of Dr. Weiss and the neurologists have the potential for improvement with BMSC treatment and be at minimal risk of any potential harm from the procedure.
5. Be over the age of 18 and capable of providing informed consent.
6. Be medically stable and able to be medically cleared by their primary care physician or a licensed primary care practitioner for the procedure. Medical clearance means that in the estimation of the primary care practitioner, the patient can reasonably be expected to undergo the procedure without significant medical risk to health.

Exclusion Criteria:

1. All patients must be capable of an adequate neurologic examination and evaluation to document the pathology. This will include the ability to cooperate with the exam.
2. Patients must be capable and willing to undergo follow up neurologic exams with the sub-investigators or their own neurologists as outlined in the protocol.
3. Patients must be capable of providing informed consent.
4. In the estimation of Dr. Weiss the BMSC collection and treatment will not present a significant risk of harm to the patient's general health or to their neurologic function. .
5. Patients who are not medically stable or who may be at significant risk to their health undergoing the procedure will not be eligible.
6. Women of childbearing age must not be pregnant at the time of treatment and should refrain from becoming pregnant for 3 months post treatment.

Primary outcomes:
measure: Change in Neurologic Function
timeFrame: 0,1,3,6 and 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Westport
country: United States
facility: MD Stem Cells
state: Connecticut
city: Coral Springs
country: United States
facility: MD Stem Cells
state: Florida
city: Dubai
country: United Arab Emirates
facility: The Saudi-German Hospital
Study officials:
affiliation: MD Stem Cells
name: Steven Levy, MD
role: STUDY_CHAIR
affiliation: Coral Springs, Florida
name: Jeffrey Weiss, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chapman CD, Frey WH 2nd, Craft S, Danielyan L, Hallschmid M, Schioth HB, Benedict C. Intranasal treatment of central nervous system dysfunction in humans. Pharm Res. 2013 Oct;30(10):2475-84. doi: 10.1007/s11095-012-0915-1. Epub 2012 Nov 8.
citation: Jiang Y, Zhu J, Xu G, Liu X. Intranasal delivery of stem cells to the brain. Expert Opin Drug Deliv. 2011 May;8(5):623-32. doi: 10.1517/17425247.2011.566267. Epub 2011 Mar 19.
citation: Bhasin A, Srivastava M, Bhatia R, Mohanty S, Kumaran S, Bose S. Autologous intravenous mononuclear stem cell therapy in chronic ischemic stroke. J Stem Cells Regen Med. 2012 Nov 26;8(3):181-9. doi: 10.46582/jsrm.0803011. eCollection 2012.
citation: Teixeira FG, Carvalho MM, Sousa N, Salgado AJ. Mesenchymal stem cells secretome: a new paradigm for central nervous system regeneration? Cell Mol Life Sci. 2013 Oct;70(20):3871-82. doi: 10.1007/s00018-013-1290-8. Epub 2013 Mar 1.
citation: Lescaudron L, Naveilhan P, Neveu I. The use of stem cells in regenerative medicine for Parkinson's and Huntington's Diseases. Curr Med Chem. 2012;19(35):6018-35.
citation: Laroni A, de Rosbo NK, Uccelli A. Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection. Immunol Lett. 2015 Dec;168(2):183-90. doi: 10.1016/j.imlet.2015.08.007. Epub 2015 Aug 18.
citation: Anbari F, Khalili MA, Bahrami AR, Khoradmehr A, Sadeghian F, Fesahat F, Nabi A. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury. Neural Regen Res. 2014 May 1;9(9):919-23. doi: 10.4103/1673-5374.133133.
citation: Weiss JN, Levy S. Neurologic Stem Cell Treatment Study (NEST) using bone marrow derived stem cells for the treatment of neurological disorders and injuries: study protocol for a nonrandomized efficacy trial. Clin Trials Degener Dis. 2016 [cited 2019 Jun 18];1:176-80.
citation: Cella D, Lai JS, Nowinski CJ, Victorson D, Peterman A, Miller D, Bethoux F, Heinemann A, Rubin S, Cavazos JE, Reder AT, Sufit R, Simuni T, Holmes GL, Siderowf A, Wojna V, Bode R, McKinney N, Podrabsky T, Wortman K, Choi S, Gershon R, Rothrock N, Moy C. Neuro-QOL: brief measures of health-related quality of life for clinical research in neurology. Neurology. 2012 Jun 5;78(23):1860-7. doi: 10.1212/WNL.0b013e318258f744. Epub 2012 May 9.
citation: Cella D, Nowinski C, Peterman A, Victorson D, Miller D, Lai JS, Moy C. The neurology quality-of-life measurement initiative. Arch Phys Med Rehabil. 2011 Oct;92(10 Suppl):S28-36. doi: 10.1016/j.apmr.2011.01.025.