Mild Cognitive ImpairmentPhase 2MCINCT01300728
Study of Intravenous Immunoglobulin in Amnestic Mild Cognitive Impairment
A Phase 2 study testing NewGam 10% IVIG in people with Mild Cognitive Impairment, run by Sutter Health at 1 site in United States.
Trial summary
Patients with mild cognitive impairment (MCI) are a group recognized at being at high risk of progressing to Alzheimer disease. Treatment of MCI with immunotherapy with intravenous immunoglobulins (IVIG) could potentially reduce the risk of progression to Alzheimer disease. Read more about this study
- Who is it for?
- Ages 50 to 84 years
- Conditions the study is for
- Mild Cognitive Impairment
- What is being tested?
- NewGam 10% IVIG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2011to 12 Mar 2020
- 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 to 84 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age from 50 to < 85 years old.
- Diagnosis of Mild Cognitive Impairment, Amnestic type (single or multi domain) according to Petersen criteria (Appendix B) and supported by a CDR score of 0.5.
- Mini-Mental State Examination (MMSE) score of 24-30, inclusive.
- Rosen Modified Hachinski Ischemic score ≤ 4.
- Willing to consent to Apolipoprotein E (ApoE) testing and agree to disclose Apolipoprotein E4 (ApoE4) status. Previous ApoE testing will be accepted.
- Receiving stable doses of medication(s) for the treatment of non-excluded medical condition(s) for at least 30 days prior to screening.
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- Ability to attend all clinical visits and have an informant capable of accompanying the subject on specific clinic visits for two years or the duration of the study.
- The subject's collaborative informant (support person) must be someone who has known the subject for at least 4 years; agrees to have at least 2 separate communications with the study participant per month for the duration of the study (one of these communications must be in person); and attends and completes the CDR interview at 8 study visits along with the subject.
- Fluency in English and evidence of adequate premorbid intellectual functioning.
- Adequate manual dexterity, visual, and auditory abilities to perform all aspects of the cognitive and functional assessments.
- Venous access suitable for repeated infusion and phlebotomy.
Who cannot join
- Has significant neurological disease, other than a-MCI that may affect cognition.
- History of clinically evident stroke or history of clinically significant carotid or vertebrobasilar stenosis or plaque.
- History of seizures, excluding febrile seizures in childhood.
- Brain MRI shows moderate or severe cortical or hippocampal atrophy.
- Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, CSF shunts, claustrophobia, metal fragments or foreign objects in the eyes, skin, or body that would contraindicate a brain MRI scan.
- Current presence of a clinically significant major psychiatric disorder according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR).
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- History of cancer within the last 5 years, with the exception of nonmetastatic basal cell carcinoma, and squamous cell carcinoma of the skin.
- Uncontrolled hypertension (diastolic BP> 100 mmHg or systolic BP> 160 mmHg, sitting).
- History or evidence of any clinically significant autoimmune disease or disorder of the immune system (eg., Crohn's Disease, Rheumatoid Arthritis)
- Women of childbearing potential.
- Weight greater than 120 kg (264 lbs).
- Excessive smoking defined as more than 20 cigarettes per day.
- History of alcohol or drug dependence or abuse as defined by DSM-IV criteria within the last 2 years.
- Severe liver or kidney disease verified by the PI review of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine.
- Known coagulopathy, thrombosis, or low platelet count.
- Known deficiency to Immunoglobulin A (IgA).
- Positive serology for Hepatitis B or C, or HIV.
- Concurrent or prior treatment with cholinesterase inhibitors and/or memantine, or Axona for cognitive enhancement. Exceptions (e.g. brief exposure to one of these medications) may be authorized if agreed upon by PI and sub-I.
- Concurrent use of anticholinergic drugs including diphenhydramine.
- Current use of anticonvulsant drugs for seizures, antiparkinson drugs, anticoagulant medications (except the use of aspirin 325 mg/day or less, plavix, aggrenox, and persantine but not for stroke).
- Concurrent use of opioid pain relievers and related synthetic derivatives.
- Use of experimental medications for AD or any other investigational medications or devices within 60 days prior to screening or within 5 half-lives of use of such a medication prior to screening, whichever is longer.
- Prior treatment with IVIG or other experimental immunotherapeutic or vaccine for MCI or AD, or prior treatment with a biological product for the treatment of a-MCI or AD.
Trial locations and contacts
1 site in 1 country.
United States1 site
Sutter Neuroscience Medical Group
Sacramento, California, 95816
About this study
Official title: A Randomized Double-Blinded Placebo-Controlled Exploratory Study of Intravenous Immunoglobulin (NewGam 10%) in Amnestic Mild Cognitive Impairment
Patients with mild cognitive impairment (MCI) are a group recognized at being at high risk of progressing to Alzheimer disease. Treatment of MCI with immunotherapy with intravenous immunoglobulins (IVIG) could potentially reduce the risk of progression to Alzheimer disease.
This study will evaluate the efficacy of intravenous immunoglobulin in patients with MCI over 24 months after the first infusion. This study will also document conversion from MCI to Alzheimer's Disease.
Read the detailed description
Screening procedures at visit 1 will take place up to 28 days prior to Visit 2 (Day 1) dosing. Screening labs and assessments will be performed during the screening period. A brain MRI will be obtained as standard of care within 6 months prior to the screening period. The first dose of study drug is administered on Day 1. Visits 2 through 6 have a ±1 day window and occur every 14 days over two months. The investigator will determine if a subject is suitable to continue following the missed infusion. Visits 7 through 12 (Month 4 through Month 24) have a ±7 day window.
All study screening data from Visit 1 including laboratory results must be reviewed for study eligibility prior to receiving first dose of study drug. Visit 2 physical exams and neurological exams prior to infusion may occur within 72 hours prior to the first infusion. Prior to infusion, a review of concomitant medications and adverse events takes place to ensure that no excluded medications have been added or medication discontinued or dose changed that were required to have been stable. If the subject continues to be eligible for enrollment, the subject will be randomized, infused with study medication and will remain in the infusion clinic for at least 4 hours following the start of the infusion for safety assessments on Visit 2 (Day 1).
- Conditions
- Mild Cognitive Impairment
- Being tested
- NewGam 10% IVIG, Placebo
- Keywords
- Intravenous immunotherapy, Conversion to Alzheimer Disease
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NewGam 10% IVIGDrug
Subjects will be randomized to receive either an infusion of IVIG at 0.4 g/kg or every 14 days for two months for a total of five infusions.
Fifty subjects will be enrolled and randomized in a 1:1 IVIG 2.0 g/kg: placebo ratio. Twenty-five subjects will receive IVIG and 25 subjects will receive placebo.
PlaceboOther
Subjects will be randomized to receive either an infusion of 0.9% saline solution (placebo) every 14 days for two months for a total of five infusions. Fifty subjects will be enrolled and randomized in a 1:1 IVIG 2.0 g/kg: placebo ratio.
| Study group | Role | What they receive |
|---|---|---|
| intravenous immunoglobulin (IVIG) | Experimental | IVIG (NewGam 10%)at 0.4 g/kg Receives: Drug: NewGam 10% IVIG |
| Saline solution | Placebo comparator | 0.9% saline solution Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized Percent Change in Ventricular Volume (APCV) as Measured by MRI
Change in ventricular volumetric as measured by MRI at baseline, 12, and 24 months following the first infusion of either 0.4 g/kg NewGam or 0.9% saline solution(placebo) every 14 days x 5.
Participants will also be classified as early MCI (EMCI) if baseline CDR-SB is less than 1.5, and late MCI (LMCI) if CDR-SB is greater than or equal to 1.5.
Measured: Baseline, 12, and 24 month MRI evaluation
Secondary outcomes (4)
Number of Participants Who Converted From Amnestic Mild Cognitive Impairment (a-MCI) to Alzheimer Disease (AD)
The National Institute of Neurological and Communicative Disorders and Stroke - Alzheimers Disease and Related Disorders Association (NINCDS-ADRDA) Alzheimer's Criteria were proposed in 1984 by NINCDS-ADRDA criteria for diagnosing Alzheimer Disease and Clinical Dementia Rating (CDR) will be used to determine conversion from a-MCI to AD.
Measured: Baseline to 24 months
Change in Ventricular Volume in Patients With Positive Cerebrospinal Fluid (CSF) Aβ1-42/CSF P-Tau181P Alzheimer Signature
Mean ventricular volume (cubic centimeters) in patients with positive cerebrospinal fluid (CSF) Aβ1-42/CSF P-Tau181P Alzheimer signature at 24 months following infusion
Measured: Baseline to 24 months following infusion
Mean Cognitive Performance at 12 Months
12 month cognitive performance in treatment (IVIG/placebo) is measured by:
- Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog)
- Scale from 0 to 85 (0 is best cognitive performance)
- Score is the sum of 12 sub-scales.
- Mini Mental State Exam (MMSE)
- Scale from 0 to 30 (30 is best cognitive performance)
- Score is the sum of 11 sub-scales.
- Clinical Dementia Rating - Sum of Boxes (CDR-SB)
- Scale is 0 to 18 (0 is best cognitive performance)
- Score is the sum of 6 sub-scales
Measured: 12 months
Mean Cognitive Performance at 24 Months
24 month cognitive performance in treatment (IVIG/placebo) is measured by:
- Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog)
- Scale from 0 to 85 (0 is best cognitive performance)
- Score is the sum of 12 sub-scales.
- Mini Mental State Exam (MMSE)
- Scale from 0 to 30 (30 is best cognitive performance)
- Score is the sum of 11 sub-scales.
- Clinical Dementia Rating - Sum of Boxes (CDR-SB)
- Scale is 0 to 18 (0 is best cognitive performance)
- Score is the sum of 6 sub-scales
Measured: 24 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2011 (estimated)
- Study start1 Jan 2011
- Primary completion12 Mar 2020
- Study completion12 Mar 2020
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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sutter Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shawn Kile, M.D., Sutter Health
- Investigators
- Shawn Kile, M.D., Principal investigator, Sutter Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01300728
- Sponsor's protocol ID
- IVIG-KILE-032010
- Acronym
- MCI
- Status last verified
- Jul 2022
- First submitted
- 22 Feb 2011
- Last updated
- 27 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Relkin NR, Szabo P, Adamiak B, Burgut T, Monthe C, Lent RW, Younkin S, Younkin L, Schiff R, Weksler ME. 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol Aging. 2009 Nov;30(11):1728-36. doi: 10.1016/j.neurobiolaging.2007.12.021. Epub 2008 Feb 21.
PubMed 18294736Kile S, Au W, Parise C, Rose K, Donnel T, Hankins A, Chan M, Ghassemi A. IVIG treatment of mild cognitive impairment due to Alzheimer's disease: a randomised double-blinded exploratory study of the effect on brain atrophy, cognition and conversion to dementia. J Neurol Neurosurg Psychiatry. 2017 Feb;88(2):106-112. doi: 10.1136/jnnp-2015-311486. Epub 2015 Sep 29.
PubMed 26420886Kile S, Au W, Parise C, Rose K, Donnel T, Hankins A, Au Y, Chan M, Ghassemi A. Five-year outcomes after IVIG for mild cognitive impairment due to alzheimer disease. BMC Neurosci. 2021 Aug 6;22(1):49. doi: 10.1186/s12868-021-00651-2.
PubMed 34362303
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-Blinded Placebo-Controlled Exploratory Study of Intravenous Immunoglobulin (NewGam 10%) in Amnestic Mild Cognitive Impairment
- ClinicalTrials.gov ID
- NCT01300728
- Acronym / sponsor ID
- MCI / IVIG-KILE-032010
- Conditions
- Mild Cognitive Impairment
- Keywords
- Intravenous immunotherapy, Conversion to Alzheimer Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Sutter HealthUniversity, hospital or other
- Study start
- 1 Jan 2011 (actual)
- Primary completion
- 12 Mar 2020 (actual)
- Study completion
- 12 Mar 2020 (actual)
- First posted
- 23 Feb 2011 (estimated)
- Results
- Posted 31 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with mild cognitive impairment (MCI) are a group recognized at being at high risk of progressing to Alzheimer disease. Treatment of MCI with immunotherapy with intravenous immunoglobulins (IVIG) could potentially reduce the risk of progression to Alzheimer disease.
This study will evaluate the efficacy of intravenous immunoglobulin in patients with MCI over 24 months after the first infusion. This study will also document conversion from MCI to Alzheimer's Disease.
Detailed description
Screening procedures at visit 1 will take place up to 28 days prior to Visit 2 (Day 1) dosing. Screening labs and assessments will be performed during the screening period. A brain MRI will be obtained as standard of care within 6 months prior to the screening period. The first dose of study drug is administered on Day 1. Visits 2 through 6 have a ±1 day window and occur every 14 days over two months. The investigator will determine if a subject is suitable to continue following the missed infusion. Visits 7 through 12 (Month 4 through Month 24) have a ±7 day window.
All study screening data from Visit 1 including laboratory results must be reviewed for study eligibility prior to receiving first dose of study drug. Visit 2 physical exams and neurological exams prior to infusion may occur within 72 hours prior to the first infusion. Prior to infusion, a review of concomitant medications and adverse events takes place to ensure that no excluded medications have been added or medication discontinued or dose changed that were required to have been stable. If the subject continues to be eligible for enrollment, the subject will be randomized, infused with study medication and will remain in the infusion clinic for at least 4 hours following the start of the infusion for safety assessments on Visit 2 (Day 1).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| intravenous immunoglobulin (IVIG) | Experimental | Drug: NewGam 10% IVIGIVIG (NewGam 10%)at 0.4 g/kg |
| Saline solution | Placebo comparator | Other: Placebo0.9% saline solution |
Who may qualify
- Ages
- 50 to 84 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age from 50 to < 85 years old.
- Diagnosis of Mild Cognitive Impairment, Amnestic type (single or multi domain) according to Petersen criteria (Appendix B) and supported by a CDR score of 0.5.
- Mini-Mental State Examination (MMSE) score of 24-30, inclusive.
- Rosen Modified Hachinski Ischemic score ≤ 4.
- Willing to consent to Apolipoprotein E (ApoE) testing and agree to disclose Apolipoprotein E4 (ApoE4) status. Previous ApoE testing will be accepted.
Key exclusion criteria (23 listed)
- Has significant neurological disease, other than a-MCI that may affect cognition.
- History of clinically evident stroke or history of clinically significant carotid or vertebrobasilar stenosis or plaque.
- History of seizures, excluding febrile seizures in childhood.
- Brain MRI shows moderate or severe cortical or hippocampal atrophy.
- Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, CSF shunts, claustrophobia, metal fragments or foreign objects in the eyes, skin, or body that would contraindicate a brain MRI scan.
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 |
|---|---|---|
| NewGam 10% IVIGSubjects will be randomized to receive either an infusion of IVIG at 0.4 g/kg or every 14 days for two months for a total of five infusions. Fifty subjects will be enrolled and randomized in a 1:1 IVIG 2.0 g/kg: placebo ratio. Twenty-five subjects will receive IVIG and 25 subjects will receive placebo. | Drug | intravenous immunoglobulin (IVIG) |
| PlaceboSubjects will be randomized to receive either an infusion of 0.9% saline solution (placebo) every 14 days for two months for a total of five infusions. Fifty subjects will be enrolled and randomized in a 1:1 IVIG 2.0 g/kg: placebo ratio. | Other | Saline solution |
Primary outcome
Annualized Percent Change in Ventricular Volume (APCV) as Measured by MRI
Time frame: Baseline, 12, and 24 month MRI evaluation
Change in ventricular volumetric as measured by MRI at baseline, 12, and 24 months following the first infusion of either 0.4 g/kg NewGam or 0.9% saline solution(placebo) every 14 days x 5. Participants will also be classified as early MCI (EMCI) if baseline CDR-SB is less than 1.5, and late MCI (LMCI) if CDR-SB is greater than or equal to 1.5.
4 secondary outcomes
Number of Participants Who Converted From Amnestic Mild Cognitive Impairment (a-MCI) to Alzheimer Disease (AD)
Time frame: Baseline to 24 months
Change in Ventricular Volume in Patients With Positive Cerebrospinal Fluid (CSF) Aβ1-42/CSF P-Tau181P Alzheimer Signature
Time frame: Baseline to 24 months following infusion
Mean Cognitive Performance at 12 Months
Time frame: 12 months
Mean Cognitive Performance at 24 Months
Time frame: 24 month
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18294736Relkin NR, Szabo P, Adamiak B, Burgut T, Monthe C, Lent RW, Younkin S, Younkin L, Schiff R, Weksler ME. 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol Aging. 2009 Nov;30(11):1728-36. doi: 10.1016/j.neurobiolaging.2007.12.021. Epub 2008 Feb 21.
- Results publication: PubMed 26420886Kile S, Au W, Parise C, Rose K, Donnel T, Hankins A, Chan M, Ghassemi A. IVIG treatment of mild cognitive impairment due to Alzheimer's disease: a randomised double-blinded exploratory study of the effect on brain atrophy, cognition and conversion to dementia. J Neurol Neurosurg Psychiatry. 2017 Feb;88(2):106-112. doi: 10.1136/jnnp-2015-311486. Epub 2015 Sep 29.
- Derived from this study: PubMed 34362303Kile S, Au W, Parise C, Rose K, Donnel T, Hankins A, Au Y, Chan M, Ghassemi A. Five-year outcomes after IVIG for mild cognitive impairment due to alzheimer disease. BMC Neurosci. 2021 Aug 6;22(1):49. doi: 10.1186/s12868-021-00651-2.
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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.
Shawn Kile, M.D. principal investigator
Sutter Health
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 NewGam 10% IVIG in people with Mild Cognitive Impairment, run by Sutter Health 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 11 inclusion and 23 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: finished, as of the sponsor's last update on 27 Oct 2022. 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 31 Mar 2016). 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?
Annualized Percent Change in Ventricular Volume (APCV) as Measured by MRI (time frame: Baseline, 12, and 24 month MRI evaluation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01300728, which also lists 3 linked publications.
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 27 Oct 2022.