HIV-associated Myelopathy
Conditions
Keywords
HIV associated myelopathy
Brief summary
The purpose of this study is to determine whether Intravenous Immunoglobulin (IVIG) is an effective treatment for HIV associated myelopathy.
Detailed description
The purpose of this study is to determine whether or not intravenous immunoglobulin (lVlg), brand name Privigen, is effective in treating a disorder called HIV-associated myelopathy (HIVM). This drug is currently not approved by the Food and Drug Administration (FDA) for treating this disorder. HIVM is a spinal cord disease that occurs at any stage of HIV infection. It is not known what causes this condition, but symptoms can include weakness in the lower body and problems with frequent urination or problems with bowel function, trouble walking or performing sexually.
Interventions
DRUGIntravenous Immunoglobulin
Intravenous Immunoglobulin - 2gr/kg over 2 days of Privigen®
DRUGPlacebo
Placebo - 2gr/kg over 2 days of saline
Sponsors
CSL Behring
David M. Simpson
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented history of HIV infection. * Age ≥ 18 * Males and females are eligible. Subjects must agree to practice birth control or abstinence. Females of child-bearing potential must have a negative urine pregnancy within 14 days prior to study entry. * Adequate baseline organ function including the following laboratory values within 14 days prior to study entry: * Adequate liver function with ALT, AST and alkaline phosphatase ≤ 5 times upper limit of normal (ULN). * Total bilirubin ≤ 2.5 mg/dL Creatinine \< 2.3 Serum vitamin B12 level ≥ 200 pg/ml * Diagnosis of HIVM by a neurologist - defined as: * \- Presence of at least two of the following symptoms: * \- Paresthesias and/or numbness in the lower extremities or in all four limbs; Weakness of the limbs, with predominance in the lower extremities; Unsteady, stiff or uncoordinated gait; Sensation of electrical shock through the back or the legs upon flexion of the neck (L'Hermitte's sign); Stiffness or spasm in the lower extremities; Urinary frequency, urgency, incontinence or retention; Fecal incontinence or retention; Sexual dysfunction with erectile impairment in men; * \- Presence of at least two of the following neurologic signs: * \- Reduction in vibratory or position sensation in the lower extremities; Hyperactive deep tendon reflexes; Abnormal response to plantar stimulation (Babinski sign); Presence of L'Hermitte sign (electrical-type sensation down the back, provoked by flexion of the neck); Weakness in the lower extremities or in all four limbs; Spastic or ataxic gait * Antiretroviral regimen stable 2 months prior to the entry of the study.
Exclusion criteria
* Presence of acute, active, opportunistic infection, except oral thrush, orogenital or rectal herpes and MAI bacteremia within 2 weeks before randomization. * Evidence of another contributing cause for myelopathy. * Women who are pregnant, breast-feeding or planning a pregnancy. * Active abuse of drugs or alcohol, which in the opinion of the investigator would interfere with the subject's ability to comply with the protocol. * Any neurologic or systemic conditions, which in the opinion of the investigator would interfere with the evaluation of the subject. * Presence of significant cardiac, pulmonary or renal disease that would place the subject at risk for the fluid and protein load of IVIg. * History of hypersensitivity to immunoglobulin, or IgA deficiency; Vaccination with live viruses within the past 90 days; Patients receiving IVIg or other immunomodulatory agent (cyclosphosphamide, azathioprine, corticosteroids, tacrolimus, cyclosporine, OKT3, plasma exchange, alpha, beta or gamma interferon) within the past 3 months. * Patients in whom muscle dynamometry can not be performed for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Strength Scores | at 2 months | Strength score as measured by pounds of force sustained in lower extremity strength. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Function | 2 months | 0 = Normal bladder function, 1 = Asymptomatic on current treatment, 2 = Urinary frequency, hesitancy, urgency, with no incontinence, 3 = Occasional urinary incontinence (once or more during the last month but not every week) or intermittent catheterization, 4 = Frequent urinary incontinence, or occasional incontinence despite regular catheterization, 5 = Daily urinary incontinence or permanent catheter |
| Bowel Function | 2 months | 0 = No bowel problems, 1 = Asymptomatic on current drug tx or constipation not requiring any tx, 2 = Constipation requiring laxative or suppositories or fecal urgency, 3 = Constipation requiring the use of an enema, 4 = Constipation requiring manual evacuation of stools or occasional fecal incontinence (once or more during the last month but not every week, 5 = Weekly fecal incontinence |
| Walking Test | at 2 months | 2 minute walking test |
| Impression of Change Score - Participant | at 2 months | The self-report measure Patient Global Impression of Change (PGIC) reflects a patient's belief about the efficacy of treatment 1. Marked improvement; 2 Moderate Improvement; 3 Minimal Improvement; 4 No Change; 5 Minimal Worsening; 6 Moderate Worsening; 7 Marked worsening |
| Impression of Change Score - Clinician | at 2 months | The clinician measure of Global Impression of Change reflects the clinician's view about the efficacy of treatment as measured by 1. Marked improvement; 2 Moderate Improvement; 3 Minimal Improvement; 4 No Change; 5 Minimal Worsening; 6 Moderate Worsening; 7 Marked worsening |
| Hughes Function Score | at 2 months | 0 = Normal strength; 1 = minor symptoms but capable of running; 2 = The subject is able to walk 30 ft. but unable to run; 3 = The subject is able to walk 30 ft. with the assistance of one person; 4 = A walker or cane; 5 = The subject is unable to walk. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from three main sources: the clinical NeuroAIDS practices of the investigators; pre-existing observational research studies (Manhattan HIV Brain Bank and the CNS HIV Antiretroviral Effects Research (CHARTER)); and via a referral network of regional HIV care providers. for a total of four years 2012-2016.
Participants by arm
| Arm | Count |
|---|---|
| Intravenous Immunoglobulin Intravenous Immunoglobulin - 2gr/kg over 2 days of Privigen® | 6 |
| Placebo Saline 2gr/kg over 2 days of saline | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Intravenous Immunoglobulin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 48 years | 58 years | 48 years |
| mean CD4+ | 620 cells/mm^3 STANDARD_DEVIATION 223 | 564 cells/mm^3 STANDARD_DEVIATION 270 | 592 cells/mm^3 STANDARD_DEVIATION 212 |
| Number of participant with undetectable Viral Load | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 1 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Strength Scores
Strength score as measured by pounds of force sustained in lower extremity strength.
Time frame: at 2 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intravenous Immunoglobulin | Strength Scores | Hip Flexion | 14.0 pounds of force | Standard Deviation 32.7 |
| Intravenous Immunoglobulin | Strength Scores | Knee Flexion | 12.4 pounds of force | Standard Deviation 14.4 |
| Intravenous Immunoglobulin | Strength Scores | Ankle Dorsiflexion | 1.7 pounds of force | Standard Deviation 8.2 |
| Intravenous Immunoglobulin | Strength Scores | Lower extremity - sum of all three | 28.2 pounds of force | Standard Deviation 49.2 |
| Placebo | Strength Scores | Lower extremity - sum of all three | 6.2 pounds of force | Standard Deviation 28.9 |
| Placebo | Strength Scores | Hip Flexion | 1.9 pounds of force | Standard Deviation 13.4 |
| Placebo | Strength Scores | Ankle Dorsiflexion | -6.0 pounds of force | Standard Deviation 5.2 |
| Placebo | Strength Scores | Knee Flexion | 10.3 pounds of force | Standard Deviation 14.5 |
Secondary
Bowel Function
0 = No bowel problems, 1 = Asymptomatic on current drug tx or constipation not requiring any tx, 2 = Constipation requiring laxative or suppositories or fecal urgency, 3 = Constipation requiring the use of an enema, 4 = Constipation requiring manual evacuation of stools or occasional fecal incontinence (once or more during the last month but not every week, 5 = Weekly fecal incontinence
Time frame: 2 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intravenous Immunoglobulin | Bowel Function | 1.3 units on a scale |
| Placebo | Bowel Function | 2.07 units on a scale |
Secondary
Hughes Function Score
0 = Normal strength; 1 = minor symptoms but capable of running; 2 = The subject is able to walk 30 ft. but unable to run; 3 = The subject is able to walk 30 ft. with the assistance of one person; 4 = A walker or cane; 5 = The subject is unable to walk.
Time frame: at 2 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intravenous Immunoglobulin | Hughes Function Score | 3 units on a scale |
| Placebo | Hughes Function Score | 3.2 units on a scale |
Secondary
Impression of Change Score - Clinician
The clinician measure of Global Impression of Change reflects the clinician's view about the efficacy of treatment as measured by 1. Marked improvement; 2 Moderate Improvement; 3 Minimal Improvement; 4 No Change; 5 Minimal Worsening; 6 Moderate Worsening; 7 Marked worsening
Time frame: at 2 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intravenous Immunoglobulin | Impression of Change Score - Clinician | 3.58 units on a scale |
| Placebo | Impression of Change Score - Clinician | 4 units on a scale |
Secondary
Impression of Change Score - Participant
The self-report measure Patient Global Impression of Change (PGIC) reflects a patient's belief about the efficacy of treatment 1. Marked improvement; 2 Moderate Improvement; 3 Minimal Improvement; 4 No Change; 5 Minimal Worsening; 6 Moderate Worsening; 7 Marked worsening
Time frame: at 2 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intravenous Immunoglobulin | Impression of Change Score - Participant | 3.58 units on a scale |
| Placebo | Impression of Change Score - Participant | 3.7 units on a scale |
Secondary
Urinary Function
0 = Normal bladder function, 1 = Asymptomatic on current treatment, 2 = Urinary frequency, hesitancy, urgency, with no incontinence, 3 = Occasional urinary incontinence (once or more during the last month but not every week) or intermittent catheterization, 4 = Frequent urinary incontinence, or occasional incontinence despite regular catheterization, 5 = Daily urinary incontinence or permanent catheter
Time frame: 2 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intravenous Immunoglobulin | Urinary Function | 2.6 units on a scale |
| Placebo | Urinary Function | 2.5 units on a scale |
Secondary
Walking Test
2 minute walking test
Time frame: at 2 months
Population: One participant in placebo group in wheelchair and unable to complete the walking test
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Immunoglobulin | Walking Test | 93.49 meters | Standard Deviation 42.57 |
| Placebo | Walking Test | 112.08 meters | Standard Deviation 102 |