A Double-Blind, Placebo Controlled Study of Intravenous Immunoglobulin for HIV-Associated Myelopathy

The purpose of this study is to determine whether Intravenous Immunoglobulin (IVIG) is an effective treatment for HIV associated myelopathy.

Study Overview

• Status: Terminated
• Conditions: HIV-associated Myelopathy
• Intervention / Treatment: Drug: Intravenous Immunoglobulin; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intravenous Immunoglobulin; Intravenous Immunoglobulin - 2gr/kg over 2 days of Privigen®	Drug: Intravenous Immunoglobulin; Intravenous Immunoglobulin - 2gr/kg over 2 days of Privigen®; Other Names: IVIG; Privigen®
PLACEBO_COMPARATOR: Placebo; Saline 2gr/kg over 2 days of saline	Drug: Placebo; Placebo - 2gr/kg over 2 days of saline; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Strength Scores	Strength score as measured by pounds of force sustained in lower extremity strength.	at 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Walking Test	2 minute walking test	at 2 months
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	2 months
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	2 months
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.	at 2 months
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	at 2 months
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	at 2 months

Collaborators and Investigators

• Sponsor: David M. Simpson
• Collaborators: CSL Behring

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (ACTUAL): September 1, 2016
• Study Completion (ACTUAL): September 1, 2016

Study Registration Dates

• First Submitted: March 21, 2012
• First Submitted That Met QC Criteria: March 21, 2012
• First Posted (ESTIMATE): March 23, 2012

Study Record Updates

• Last Update Posted (ACTUAL): April 13, 2018
• Last Update Submitted That Met QC Criteria: April 10, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: HIV associated myelopathy
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Hematologic Diseases; Spinal Cord Diseases; Bone Marrow Diseases; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: GCO 10-1108; HS#: 11-02029