Status:
TERMINATED
Stem Cell Transplantation for Stiff Person Syndrome (SPS)
Lead Sponsor:
Northwestern University
Conditions:
Stiff-Person Syndrome
Eligibility:
All Genders
18-60 years
Phase:
PHASE1
PHASE2
Brief Summary
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-myeloa...
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-...
Eligibility Criteria
Inclusion
- 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 intravenous immunoglobulin (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
- 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
- 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 spinocerebellar ataxia (SCA) 1, SCA 2, SCA 3, SCA 6, SCA 7 or SCA 8 mutation
Exclusion
- 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
- Left ventricular ejection fraction (LVEF) \< 45% or ischemic coronary artery disease on dobutamine stress echocardiogram
- Diffusing capacity of the lungs for carbon monoxide (DLCO) \< 60% predicted
- Serum creatinine \> 2.0 mg/dl
- Bilirubin \>2.0 mg/dl
- Platelet count \< 100,000 / ul, white blood cell count (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 gamma-aminobutyric acid (GABA)-A receptor associated protein, or synaptophysin, or gephyrin, or GABA-transaminase
Key Trial Info
Start Date :
October 1 2014
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
August 30 2019
Estimated Enrollment :
23 Patients enrolled
Trial Details
Trial ID
NCT02282514
Start Date
October 1 2014
End Date
August 30 2019
Last Update
January 27 2021
Active Locations (1)
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1
Northwestern University
Chicago, Illinois, United States, 60611