Alzheimer's DiseasePhase 2NCT00299988
Phase II Study of Intravenous Immunoglobulin (IVIg) for Alzheimer's Disease
A Phase 2 study testing Intravenous Immunoglobulin in people with Alzheimer's Disease, run by Weill Medical College of Cornell University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Intravenous Immunoglobulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2006to Apr 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- Known coagulopathy or platelet counts < 100,000.
- Positive serology for Hepatitis B or C, or HIV.
- Active migraines or frequent headaches (3 or more times per week).
- Taking immunosuppressive drugs.
- Chronic (more than thrice weekly) use of non-steroidal anti-inflammatory drugs (NSAIDs), excluding aspirin 81 milligrams daily.
- Received an investigational treatment for AD within 3 months of study entry.
- A history of or current disorder or disease that in a physician co-investigator's judgment may impede the subject's participation in the study, pose immoderate risk to the patient or confound the results of the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Weill Medical College of Cornell University
New York, New York, 10021
About this study
Official title: A Placebo-controlled, Randomized, Double-Blind Phase II Clinical Study of Gammagard Intravenous Immunoglobulin (IVIg) for Treatment of Mild to Moderate Alzheimer's Disease
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.
Read the detailed description
Abnormal processing of the beta-amyloid protein is thought to be an early and causative event in the pathogenesis of Alzheimer's disease (AD). Immunotherapy targeting beta amyloid (Aβ) has demonstrated a remarkable capacity to arrest and even reverse elements of AD brain pathology. Intravenous Immunoglobulin (IVIg) is a medication obtained from the pooled plasma of healthy human blood donors that contains natural anti-amyloid antibodies and exhibits potent central nervous system anti-inflammatory properties. IVIg has been FDA-approved and used for more than 25 years in patients with a variety of immune deficiency and autoimmune diseases and has an established safety record, but is not FDA-approved for the treatment of AD.
A total of 24 patients, males and females 50 years of age and older, with mild to moderate Alzheimer's disease (AD) will be enrolled in this research study. To be eligible, patients must meet the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD. After written informed consent is obtained, subjects will go through a screening process to determine if he or she meets the inclusion criteria. Screening procedures include medical history, blood and urine tests, neurologic exam, chest x-ray and MRI. 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.
To be eligible for this research study, patients must be taking a stable dose of an approved AD medication for at least 3 months prior to entering this study or be unable to take these medications. The design of this protocol is that of an add-on study and we will recommend patients continue to take any FDA-approved AD medications they are taking at study entry.
Subjects' participation in the study will last approximately 19 months, including screening and baseline procedures, treatment with study drug and a follow-up visit 1 ½ months after finishing treatment, plus a visit for blood tests 6 months after the last infusion in the study. This research study requires that the patient have another person, (such as a spouse, child, other relative, close friend, aide or other professional caregiver), who will accompany the patient to each clinic visit.
Subjects will be randomized to a treatment group for 6 months of infusions of IVIg or placebo. The treatment groups compare different doses and frequencies of treatment. Patients will have a 33% chance of receiving placebo.
Blood will be obtained from subjects every two weeks and examined in our research laboratories to obtain more information about IVIg's biological effects. Cerebrospinal fluid will be obtained by lumbar puncture twice over the course of the study for the same purpose. Patients will be asked to allow a portion of a blood sample to be used for Apolipoprotein E (APOE) testing and banked for genetic research testing related to AD and aging, but do not have to participate in the testing or allow their blood sample to be stored in order to take part in the study.
Cognitive testing will be carried out at baseline and every three months over a period of 18 months. Results of cognitive testing will constitute the primary endpoint of this study. Positron Emission Tomography (PET) imaging substudies will be performed at two time points during the study. Safety laboratories and assessments will be carried out at regular intervals. Subjects will not be responsible for any research study-related costs but will be responsible for the costs of evaluations required to establish diagnosis.
- Conditions
- Alzheimer's Disease
- Being tested
- Intravenous Immunoglobulin, Placebo
- Keywords
- Immunotherapy, Amyloid beta protein, Antibodies, Alzheimer's, Dementia
- Medical subject headings
- Alzheimer Disease, Plaque, Amyloid, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous ImmunoglobulinDrug
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| IVIG | Experimental | ivig Receives: Drug: Intravenous Immunoglobulin |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2006 (estimated)
- Study startFeb 2006
- Primary completionJan 2009
- Study completionApr 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- Baxter BioScience, National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Norman R Relkin, M.D., Ph.D., Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00299988
- Sponsor's protocol ID
- 0512008265
- Status last verified
- Nov 2019
- First submitted
- 3 Mar 2006
- Last updated
- 11 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo-controlled, Randomized, Double-Blind Phase II Clinical Study of Gammagard Intravenous Immunoglobulin (IVIg) for Treatment of Mild to Moderate Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT00299988
- Acronym / sponsor ID
- 0512008265
- Conditions
- Alzheimer's Disease
- Keywords
- Immunotherapy, Amyloid beta protein, Antibodies, Alzheimer's, Dementia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- Baxter BioScience, National Institutes of Health (NIH)
- Study start
- Feb 2006
- Primary completion
- Jan 2009 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 7 Mar 2006 (estimated)
- Results
- Posted 11 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Abnormal processing of the beta-amyloid protein is thought to be an early and causative event in the pathogenesis of Alzheimer's disease (AD). Immunotherapy targeting beta amyloid (Aβ) has demonstrated a remarkable capacity to arrest and even reverse elements of AD brain pathology. Intravenous Immunoglobulin (IVIg) is a medication obtained from the pooled plasma of healthy human blood donors that contains natural anti-amyloid antibodies and exhibits potent central nervous system anti-inflammatory properties. IVIg has been FDA-approved and used for more than 25 years in patients with a variety of immune deficiency and autoimmune diseases and has an established safety record, but is not FDA-approved for the treatment of AD.
A total of 24 patients, males and females 50 years of age and older, with mild to moderate Alzheimer's disease (AD) will be enrolled in this research study. To be eligible, patients must meet the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD. After written informed consent is obtained, subjects will go through a screening process to determine if he or she meets the inclusion criteria. Screening procedures include medical history, blood and urine tests, neurologic exam, chest x-ray and MRI. 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.
To be eligible for this research study, patients must be taking a stable dose of an approved AD medication for at least 3 months prior to entering this study or be unable to take these medications. The design of this protocol is that of an add-on study and we will recommend patients continue to take any FDA-approved AD medications they are taking at study entry.
Subjects' participation in the study will last approximately 19 months, including screening and baseline procedures, treatment with study drug and a follow-up visit 1 ½ months after finishing treatment, plus a visit for blood tests 6 months after the last infusion in the study. This research study requires that the patient have another person, (such as a spouse, child, other relative, close friend, aide or other professional caregiver), who will accompany the patient to each clinic visit.
Subjects will be randomized to a treatment group for 6 months of infusions of IVIg or placebo. The treatment groups compare different doses and frequencies of treatment. Patients will have a 33% chance of receiving placebo.
Blood will be obtained from subjects every two weeks and examined in our research laboratories to obtain more information about IVIg's biological effects. Cerebrospinal fluid will be obtained by lumbar puncture twice over the course of the study for the same purpose. Patients will be asked to allow a portion of a blood sample to be used for Apolipoprotein E (APOE) testing and banked for genetic research testing related to AD and aging, but do not have to participate in the testing or allow their blood sample to be stored in order to take part in the study.
Cognitive testing will be carried out at baseline and every three months over a period of 18 months. Results of cognitive testing will constitute the primary endpoint of this study. Positron Emission Tomography (PET) imaging substudies will be performed at two time points during the study. Safety laboratories and assessments will be carried out at regular intervals. Subjects will not be responsible for any research study-related costs but will be responsible for the costs of evaluations required to establish diagnosis.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IVIG | Experimental | Drug: Intravenous Immunoglobulinivig |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous Immunoglobulin | Drug | IVIG |
| Placebo | Other | Placebo |
Primary outcome
ADAS-Cog
Time frame: 12 months
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.
CGIC
Time frame: 12 months
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Norman R Relkin, M.D., Ph.D. principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intravenous Immunoglobulin in people with Alzheimer's Disease, run by Weill Medical College of Cornell University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ADAS-Cog (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2019.