Phase II Study of Intravenous Immunoglobulin (IVIg) for Alzheimer's Disease

NCT00299988 | Terminated Phase 2 Results DMC

• 1 other identifier: 0512008265
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The overall goal of this double-blind Phase II study is to evaluate the safety, efficacy and biological mechanisms of action of Intravenous Immunoglobulin (IVIg) in the treatment of mild to moderate stage Alzheimer's disease (AD). IVIg contains antibodies against the amyloid beta protein that is the central component of the AD senile plaque. It is hypothesized that IVIg treatment will reduce the levels of beta amyloid in the brain and improve cognitive abilities relative to placebo. A total of 24 patients with mild to moderate AD capable of giving informed consent will be randomly assigned to receive either IVIg (16 patients)or saline placebo (8 patients) for six months. This study includes comparison of four dosing regimens of IVIg. Cognitive, behavioral and functional measures will be collected at baseline, three months and six months of treatment. Plasma samples will be collected before and after infusions. Subjects will undergo a lumbar puncture before and after the six months of treatment for cerebrospinal fluid (CSF) biomarker analyses. In addition, Positron Emission Tomography (PET) imaging substudies will be performed at two time points during the study. Following the initial 6 month placebo-controlled period, all participants have the opportunity to receive IVIg for an additional 12 month period in an extension study.

Conditions

Alzheimer's Disease

Keywords

Immunotherapy; Amyloid beta protein; Antibodies; Alzheimer's; Dementia

Outcome Measures

Primary Outcomes (2)

• ADAS-Cog

  The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is a brief neuropsychological assessment used to assess the severity of cognitive symptoms of dementia. It is one of the most widely used cognitive scales in clinical trials and is considered to be the "gold standard" for assessing antidementia treatments. The ADAS-Cog range from 0 to 70, where higher scores indicate greater cognitive dysfunction.

  12 months

• CGIC

  The Clinical Global Impression of Change focuses on clinicians' observations of change in the patient's cognitive, functional, and behavioral performance since the beginning of a trial. It relies on both direct examination of the patient and interview of informants. Unlike a targeted symptom scale, it takes into account a subject's overall function in the cognitive, behavioral and functional activity domains. Scoring is based on an interview with the caregiver and examination of the patient by an independent evaluator, without consulting other information such as cognitive test results. The CGIC range from 1 to 7, where 1=very much improved since the initiation of treatment; 4=no change from baseline; 7=very much worse since the initiation of treatment.

  12 months

Study Arms (2)

IVIG

EXPERIMENTAL

ivig

Drug: Intravenous Immunoglobulin

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Intravenous Immunoglobulin DRUG

IVIG

Placebo OTHER

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of probable Alzheimer's disease (AD) of mild to moderate severity (as determined by a Mini Mental State Examination (MMSE) score of 14 - 26 inclusive).
• Ability to give informed consent, designate a decision-maker or have an already recognized decision-maker (such as a legal guardian or health care proxy).
• Ability to comply with testing and infusion regimen.
• An able caregiver willing to participate (such as a spouse, child, other relative, close friend, aide or other professional caregiver closely involved in helping the patient take care of himself/herself).
• Venous access suitable for repeated infusion and phlebotomy.
• On stable doses of approved AD medications for at least 3 months.
• As applicable, on stable doses of psychoactive medications (e.g. antidepressants, antipsychotics) for at least 6 weeks.
• Neuroimaging performed after symptom onset consistent with the patient's diagnosis.
• Clinical laboratory values within normal limits or if abnormal, judged clinically insignificant by the Principal Investigator.
• Women who want to take part in this study must either be post-menopausal, surgically sterilized or agree to avoid becoming pregnant during the entire period of their participation in this study.

You may not qualify if:

• Non-Alzheimer dementia.
• Active renal disease.
• Abnormally high serum viscosity levels.
• Immunoglobulin A (IgA) deficiency.
• Untreated congestive heart failure, unstable angina or a history of recent myocardial infarction.
• Unstable arrhythmia.
• Untreated or poorly controlled hypercholesterolemia.
• Untreated or poorly controlled hypertension.
• Poorly controlled diabetes.
• Thrombosis (central or peripheral) in the past year.
• Modified Hachinski score \> 5.
• Active cancer diagnosis, except basal cell carcinoma.
• Active autoimmune or neuroimmunologic disorder.
• History of IVIg treatment in past 6 months.
• Untreated major depression or other major psychiatric disorders.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Baxter BioScience: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Plaque, Amyloid; Dementia

Interventions

Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was terminated due to the results from another phase III study with IVIG: PMC5409846, NCT00818662

Results Point of Contact

• Title: Norman Relkin, MD, PhD
• Organization: Weill Cornell Medical College

nrelkin@med.cornell.edu

212-746-9882

Study Officials

• Norman R Relkin, M.D., Ph.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2006
• First Posted: March 7, 2006
• Study Start: February 1, 2006
• Primary Completion: January 1, 2009
• Study Completion: April 1, 2010
• Last Updated: December 11, 2019
• Results First Posted: December 11, 2019

Record last verified: 2019-11

Locations

US (1)