We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Stem Cell Transplantation for Stiff Person Syndrome (SPS) (SPS)

This study is currently recruiting participants.
Verified March 2017 by Richard Burt, MD, Northwestern University
Sponsor:
ClinicalTrials.gov Identifier:
NCT02282514
First Posted: November 4, 2014
Last Update Posted: July 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Richard Burt, MD, Northwestern University
  Purpose

Non-myeloablative regimens (as the investigators use herein) are designed to maximally suppress the immune system without destruction of the bone marrow stem cell compartment.

When using a non-myeloablative regimen recovery occurs without infusion of stem cells and the stem cells are autologous. While not necessary for recovery, stem cell infusion may shorten the interval of neutropenia and attendant complications. Thus in reality there is no transplant only an autologous supportive blood product.

Based on our encouraging results of non-myeloablative hematopoietic stem cell transplantation, for patients with multiple sclerosis and chronic inflammatory demyelinating polyneuropathy, the investigators will investigate the role of non-myeloablative hematopoietic stem cell transplantation for patients with SPS who require assistance to ambulate.


Condition Intervention Phase
Stiff Person Syndrome Biological: Autologous Hematopoietic Stem Cell Transplantation Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Non-myeloablative Hematopoietic Stem Cell Transplantation for Stiff Person Syndrome (SPS) and Anti-GAD Antibody Variants: Progressive Encephalomyelitis With Rigidity and Myoclonus (PERM), and Adult Onset Autoimmune Anti-GAD Positive Cerebellar Ataxia

Resource links provided by NLM:


Further study details as provided by Richard Burt, MD, Northwestern University:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: Up to 5 years ]

Secondary Outcome Measures:
  • Decrease (50%) and complete discontinuation of muscle relaxation anti-spasmatic medications [ Time Frame: Up to 5 years ]
  • Improvement of Chronic Pain Acceptance Questionnaire (CPAQ) [ Time Frame: Up to 5 years ]
    Improvement is defined as a statistically significant change in the CPAQ score

  • Timed ambulation [ Time Frame: Up to 5 years ]
    Improvement is defined as a statistically significant change in the timed ambulation score

  • Activities of Daily Living ((Barthel Index) [ Time Frame: Up to 5 years ]
    Improvement is defined as a statistically significant change in Barthel Index score

  • Short-form 36 quality of life questionnaire (SF-36 QOL) [ Time Frame: Up to 5 years ]
    Improvement is defined as a statistically significant change in SF-36 QOL score

  • Rankin Functional Scale [ Time Frame: Up to 5 years ]
    Improvement is defined as a statistically significant change in Rankin Functional Scale score


Estimated Enrollment: 40
Study Start Date: October 2014
Estimated Study Completion Date: October 2021
Estimated Primary Completion Date: October 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Autologous Hematopoietic Stem Cell Transplantation
The stem cells will be collected from patient's blood during mobilization. Then the patient will be given high dose chemotherapy in accordance with approved recommendations for use in conditioning regimens for stem cell transplant in autoimmune diseases. Autologous Hematopoietic Stem Cell Transplantation is to re-infuse immature cells that can re-establish blood production and patient's immune system.
Biological: Autologous Hematopoietic Stem Cell Transplantation
The stem cells will be collected from patient's blood during mobilization. Then the patient will be given high dose chemotherapy in accordance with approved recommendations for use in conditioning regimens for stem cell transplant in autoimmune diseases. Autologous Hematopoietic Stem Cell Transplantation is to re-infuse immature cells that can re-establish blood production and patient's immune system.
Other Name: Autologous Hematopoietic Stem Cell Injection

Detailed Description:

Pre-study Testing

1. History and physical; 2. Electrocardiogram (EKG); 3. Dobutamine stress echocardiogram; 4. High-resolution computed tomography of the chest (HRCT); 5. Blood draw for laboratory tests- these tests will include a complete blood count, evaluating liver and kidney function, assessing immune system, tissue typing, and checking for certain germs that can cause infections, including a pregnancy test for females and prostate-specific antigen (PSA) for male as well as testing for HIV; 6. Pulmonary Function Test (PFT); 7. Electromyography (EMG); 8. Magnetic Resonance Imaging (MRI) of the Abdomen and Pelvis; 9. Magnetic Resonance Imaging (MRI) of the Spinal Cord; 10. Magnetic Resonance Imaging (MRI) of the Brain with Gadolinium (only if PERM of cerebellar ataxia); 11. Colonoscopy; 12. Mammogram (if female; 13. Timed ambulation; 14. Quality of Life Questionnaires [ Short Form (36) Health Survey (SF36) and Barthel Index]; 15. Chronic Pain Acceptance Questionnaire (CPAQ);16. Rankin Functional Scale; 17. Modified Ashworth Scale;18. PCA-1, PCA-2 antibody ( only if cerebellar ataxia); 19. Spinocerebellar ataxia (SCA) 1, 2, 3, 4, 5, 6, 7, 8 genes (only if ataxia)

Study Treatment

Stem Cell Collection-Cyclophosphamide 2.0 gm/m2 will be given on day 0, G-CSF 5-10 mcg/kg/day SQwill start on day +5 and will continue until apheresis is discontinued. Apheresis will begin when the ANC > 1.0 x 109/L and continue until >2.0 x 106 CD34+ cells/kg patient weight are cryopreserved. A 10-15 liter apheresis will be performed unless stopped earlier for clinical judgment of toxicity (e.g., numbness, tetany). A maximum of four apheresis will be performed.

Conditioning regimen Cyclophosphamide 50 mg/kg/day will be given IV over 1 hour in 250 cc of normal saline on day -5, -4, -3, and -2. If actual weight is < ideal weight, cyclophosphamide will be given based on actual weight. If actual weight is > ideal weight, cyclophosphamide will be given as adjusted ideal weight. Adjusted ideal weight = ideal weight + 40% x actual weight minus ideal weight.

Mesna 50mg/kg/day will be given IV over 24 hours in 250 cc of normal saline or D5W. Weight base is calculated same as cyclophosphamide as above.

ATG (rabbit) 0.5 mg/kg on day -5; 1mg/kg on day -4 and -3; 1.5 mg/kg on day -2 and -1 (total 5.5mg/kg, no dose adjustment) will be given IV over 10 hours in 250 cc of normal saline beginning at least 1 hour after infusion of cyclophosphamide. Premedicate with acetaminophen 650 mg po and diphenhydramine 25 mg po/IV 30 minutes before the infusion. An in-line 0.22 µm filter should be used for ATG administration.

Methylprednisolone A suggested dose of 250mg IV should be administered 30 minutes before each ATG infusion.

Hydration A suggested rate of 125 cc/hr NS should be given starting 6 hours before cyclophosphamide and continue until 24 hours after the last cyclophosphamide dose.The rate of hydration will be aggressively adjusted in order to avoid fluid overload. BID weights will be obtained. Amount of fluid can be modified based on patient's fluid status. Minimum target urine output is 2 liters/m2/day

G-CSF 5 mcg/kg/day SQ will be continued until the absolute neutrophil counts reach at least 500/µl.

Rituxan 500 mg will be given IV on the day before the first dose of ATG and the day after stem cell infusion.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of Stiff-person Syndrome and

    • Age between 18 and 60 years old
    • Failure of medically tolerable doses (20-40 mg/day) of diazepam
    • Failure of either IVIG and or plasmapheresis
    • Stiffness in the axial muscles, prominently in the abdominal and thoracolumbar paraspinal muscle leading to a fixed deformity (hyperlordosis)
    • Superimposed painful spasms precipitated by unexpected noises, emotional stress, tactile stimuli
    • Confirmation of the continuous motor unit activity in agonist and antagonist muscles by electromyography when off diazepam and anti-spasmatic medications
    • Absence of neurological or cognitive impairments that could explain the stiffness
    • Inability to run or walk, or abnormal gait
  2. Diagnosis of a SPS variant— Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM) defined as:

    Acute onset of painful rigidity and muscle spasms in the limbs and trunk

    • Brainstem dysfunction (nystagmus, opsoclonus, ophthalmoparesis, deafness, dysarthria, dysphagia)
    • Profound autonomic disturbance.
    • Positive serology for GAD65 (or amphiphysin) autoantibodies, assessed by immunocytochemistry, western blot or radioimmunoassay (>1000 u/ml)
    • MRI may show increased signal intensity throughout the spinal cord and the brainstem
  3. Diagnosis of a SPS variant - anti-GAD positive cerebellar ataxia

    • Subacute or chronic onset of cerebellar symptoms—gait or limb ataxia, dysarthria, nystagmus
    • Positive serology for GAD65 (or amphiphysin) autoantibodies, assessed by immunocytochemistry, western blot or radioimmunoassay (>1000 u/ml)
    • Anti-GAD antibody in cerebrospinal fluid
    • Abnormal MRI imaging of brainstem or cerebellum other than cerebellar atrophy
    • Negative history of toxin or alcohol
    • Absence of Vitamin B12 or Vitamin E deficiency
    • Absence of positive HIV, syphilis or whipple disease
    • Absence of consanguinity, positive family history for ataxia or positive genetic screen for SCA1, SCA2, SCA3, SCA6, SCA 7 or SCA8 mutation

Exclusion Criteria:

  • Current or prior history of a malignancy or paraneoplastic syndrome
  • Inability to sign and understand consent and be compliant with treatment
  • Positive pregnancy test
  • Inability to or comprehend irreversible sterility as a possible side effect
  • Amphiphysin antibody positive
  • LVEF < 45% or ischemic coronary artery disease on dobutamine stress echocardiogram
  • DLCO < 60% predicted
  • Serum creatinine > 2.0 mg/dl
  • Bilirubin >2.0 mg/dl
  • Platelet count < 100,000 / ul, WBC < 1,500 cells/mm3
  • History of toxin or alcohol abuse
  • History of Vitamin B12 or Vitamin E deficiency
  • Positive HIV, syphilis, or whipple disease
  • Consanguinity, positive family history for ataxia or positive genetic screen for SCA1, SCA2, SCA3, SCA6, SCA 7 or SCA8 mutation (if ataxia present)
  • Absence of at least one SPS associated antibody such as anti-GAD, or GABA-A receptor associated protein, or synaptophysin, or gephyrin, or GABA-transaminase
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02282514


Contacts
Contact: Kathleen Quigley 312-695-4960 k-quigley@northwestern.edu

Locations
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Richard Burt, MD    312-695-4960    rburt@northwestern.edu   
Sub-Investigator: Senda Ajroud Driss, MD         
Sub-Investigator: Jeffrey Allen, MD         
Sub-Investigator: Robert Sufit, MD         
Sub-Investigator: Teepu Siddique, MD         
Sub-Investigator: Roumen Balabanov, MD         
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Richard Burt, MD Northwestern University
  More Information

Responsible Party: Richard Burt, MD, Professor, Division Chief, Northwestern University
ClinicalTrials.gov Identifier: NCT02282514     History of Changes
Other Study ID Numbers: DIAD.SPS.2014
First Submitted: October 30, 2014
First Posted: November 4, 2014
Last Update Posted: July 21, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Richard Burt, MD, Northwestern University:
autoimmune diseases
stem cells
autologous hematopoietic stem cell transplantation
Stiff Person Syndrome (SPS)

Additional relevant MeSH terms:
Syndrome
Stiff-Person Syndrome
Disease
Pathologic Processes
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Neuromuscular Diseases
Autoimmune Diseases
Immune System Diseases