Mild Cognitive ImpairmentPhase 2NCT03319810
Effect of IVIG on Cerebral and Retinal Amyloid in Mild Cognitive Impairment Due to Alzheimer Disease
A Phase 2 study testing Octagam 10% in people with Mild Cognitive Impairment, run by Sutter Health at 1 site in United States.
Trial summary
This is a proof of concept study to determine if changes in brain amyloid levels are evident three months after infusion of 0.4 g/kg of IVIG every 14 days x 5 infusions. Amyloid levels will be measured by Florbetapir PET and retinal scan. 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?
- Octagam 10%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Jan 2018to 19 Jul 2018
- 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 50 to <85 years.
- Evidence of amyloid pathology on Florbetapir PET at screening.
- Diagnosis of MCI due to AD based on NIA-AA criteria. (APPENDIX A)
- MRI brain (with past 24 months) which shows evidence of mild hippocampal atrophy and/or bilateral parietal atrophy.
- CDR score of 0.5
- Mini-Mental State Examination (MMSE) score of 24-30, inclusive.
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- Rosen Modified Hachinski Ischemic score ≤4.
- Receiving stable doses of medication(s) for the treatment of non-excluded medical condition(s) for at least 30 days prior to screening. Cholinesterase inhibitors and memantine are allowed if doses have stable been least 30 days prior to screening.
- Agree to refrain from participating in any treatment or clinical trial targeting amyloid for the duration of the study.
- Agree to refrain from taking any herbal supplement considered to enhance cognition unless approved by the investigator for the duration of the study.
- Ability to attend all clinical visits and have an informant capable of accompanying the subject on specific clinic visits.
- The subject's collaborative informant (support person) must be someone who has known the subject for at least 4 years and has had approximately 2 or more separate communications with the study participant per month (at least one of these communications in person).
- 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 infusions and phlebotomy.
- In the opinion of the investigator, the subject and informant will be compliant and have a high probability of completing the study, including all scheduled evaluations and required tests.
Who cannot join
- Has significant neurological disease other than MCI that in the opinion of the investigator 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.
- History of screening visit brain MRI scan indicative of any other significant abnormality, including but not limited to multiple microhemorrhages (2 or more), history or evidence of a single prior hemorrhage > 1 cm3, multiple lacunar infarcts (2 or more) or evidence of a single prior infarct > 1 cm3, evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions of significance as determined by the PI (e.g., arachnoid cysts or brain tumors such as meningioma).
- Brain MRI shows moderate or severe cortical or hippocampal atrophy.
- Sensitivity to Florbetapir.
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- Other present/planned ionized radiation that, in combination with planned exposure to PET ligands for this study, would result in cumulative exposure that would exceed recommended limits.
- Ophthalmologic condition that would interfere with retinal amyloid imaging.
- Current presence of a clinically significant major psychiatric disorder (e.g., Major Depressive Disorder) according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) or symptom (e.g., hallucinations) that in the opinion of the investigator could affect the subject's ability to complete the study.
- Current clinically significant systemic illness that is likely to result in deterioration of the subject's condition or affect the subject's safety during the study including but not limited to renal failure or myocardial infarction.
- 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 (e.g., Crohn's Disease, Rheumatoid Arthritis)
- Clinically significant infection within the last 30 days (e.g., chronic persistent or acute infection (eg, upper respiratory infection [URI], urinary tract infection [UTI]).
- Female subjects of childbearing potential.
- Other clinically significant abnormality on physical, neurological, laboratory, vital signs or ECG examination (e.g., atrial fibrillation) that could compromise the study or be detrimental to the subject.
- 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 ALT, AST and creatinine.
- Known coagulopathy, thrombosis, or low platelet count.
- Hemoglobin less than 11 g/dL.
- Known deficiency to IgA.
- Positive serology for Hepatitis B or C, or HIV.
- History of anti-amyloid treatment, immunotherapy, or other experimental treatment for MCI or Alzheimer disease.
- Concurrent use of anticholinergic drugs including diphenhydramine.
- Current use of 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Sutter Neuroscience Medical Group
Sacramento, California, 95816
About this study
Official title: Proof of Concept of the Effect of Intravenous Immunoglobulin on Cerebral and Retinal Amyloid in Mild Cognitive Impairment Due to Alzheimer Disease
This is a proof of concept study to determine if changes in brain amyloid levels are evident three months after infusion of 0.4 g/kg of IVIG every 14 days x 5 infusions. Amyloid levels will be measured by Florbetapir PET and retinal scan.
Read the detailed description
Study design:
This is a single center, open label, proof of concept, out-patient study. Subjects will undergo Florbetapir PET and have retinal amyloid levels measured, receive an infusion of IVIG at 0.4 g/kg every 14 days for a total of five infusions, and repeat PET and retinal amyloid measures three months after the first infusion.
Subject population:
The study population will consist of male and female subjects diagnosed with mild cognitive impairment (MCI) due to Alzheimer disease (AD).
Estimated study duration:
The duration of each study subject is approximately 4 months, including one screening visit over a period of approximately 28 days, 5 days of infusions over a 2-month period of time, and a follow-up visit at 3 months after the first infusion.
Description of study drug:
Octagam is an FDA approved 10% human normal immunoglobulin solution ready for intravenous administration.
Study drug dosage:
The dose level of IVIG at 0.4 g/kg will be administered by IV infusion once every 14 days for two months.
Concomitant therapy:
Concomitant medications will be assessed at all study visits. Concomitant medications are prescribed or over-the-counter medications and should be consistent with the inclusion/exclusion criteria. Concomitant medication appropriate to the subject's condition may be prescribed during the course of the study with the exception of those listed above.
Routine vaccinations (i.e., flu vaccination) with commercially available therapeutics are permitted but must not be given within four weeks before or after the administration of the study drug.
Evaluations by visit:
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. 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 a missed infusion. Visit 7 has 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. Prior to infusion, a review of concomitant medications and AEs takes place. If the subject continues to be eligible for enrollment, the subject will be infused with study medication and will remain in the infusion clinic for at least 1 hour following the infusion for safety assessments on Visit 2 (Day 1), and 15 minutes for the subsequent visits.
- Conditions
- Mild Cognitive Impairment
- Being tested
- Octagam 10%
- Keywords
- MCI, Alzheimer Disease, AD
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Octagam 10%Biological
FDA approved human normal immunoglobulin solution ready for intravenous administration
| Study group | Role | What they receive |
|---|---|---|
| infusion of IVIG | Experimental | Not described Receives: Biological: Octagam 10% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Baseline Standard Uptake Ratio Values (SUVr) of Florbetapir PET at 3 Months
Amyloid deposition in the brain is thought to lead to the development of cognitive decline and conversion to AD. Each participant's amyloid burden can also be quantified through the computation of a Standard Uptake Value ratio (SUVr).
Measured: Baseline to 3 months
Change in Baseline Retinal Amyloid Imaging (RAI) at 3 Months
This is a noninvasive imaging technique that can detect amyloid-beta deposition in the retinas of the eye.
Measured: Baseline to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2017
- Study start4 Jan 2018
- Primary completion19 Jul 2018
- Study completion19 Jul 2018
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 (1)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
- Not applicable
- Intervention model
- Single group
- Model description
- This is a single center, open label, proof of concept, out-patient study.
- Masking
- None (open label)
- Enrolment
- 5 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, MD, Principal investigator, Sutter HealthCarol Parise, PhD, Study director, Sutter Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03319810
- Sponsor's protocol ID
- SIMR_Kile_IVIG POC
- Status last verified
- Jun 2019
- First submitted
- 11 Oct 2017
- Last updated
- 25 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kile 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 26420886
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proof of Concept of the Effect of Intravenous Immunoglobulin on Cerebral and Retinal Amyloid in Mild Cognitive Impairment Due to Alzheimer Disease
- ClinicalTrials.gov ID
- NCT03319810
- Acronym / sponsor ID
- SIMR_Kile_IVIG POC
- Conditions
- Mild Cognitive Impairment
- Keywords
- MCI, Alzheimer Disease, AD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Sutter HealthUniversity, hospital or other
- Study start
- 4 Jan 2018 (actual)
- Primary completion
- 19 Jul 2018 (actual)
- Study completion
- 19 Jul 2018 (actual)
- First posted
- 24 Oct 2017 (actual)
- Results
- Posted 16 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a proof of concept study to determine if changes in brain amyloid levels are evident three months after infusion of 0.4 g/kg of IVIG every 14 days x 5 infusions. Amyloid levels will be measured by Florbetapir PET and retinal scan.
Detailed description
Study design:
This is a single center, open label, proof of concept, out-patient study. Subjects will undergo Florbetapir PET and have retinal amyloid levels measured, receive an infusion of IVIG at 0.4 g/kg every 14 days for a total of five infusions, and repeat PET and retinal amyloid measures three months after the first infusion.
Subject population:
The study population will consist of male and female subjects diagnosed with mild cognitive impairment (MCI) due to Alzheimer disease (AD).
Estimated study duration:
The duration of each study subject is approximately 4 months, including one screening visit over a period of approximately 28 days, 5 days of infusions over a 2-month period of time, and a follow-up visit at 3 months after the first infusion.
Description of study drug:
Octagam is an FDA approved 10% human normal immunoglobulin solution ready for intravenous administration.
Study drug dosage:
The dose level of IVIG at 0.4 g/kg will be administered by IV infusion once every 14 days for two months.
Concomitant therapy:
Concomitant medications will be assessed at all study visits. Concomitant medications are prescribed or over-the-counter medications and should be consistent with the inclusion/exclusion criteria. Concomitant medication appropriate to the subject's condition may be prescribed during the course of the study with the exception of those listed above.
Routine vaccinations (i.e., flu vaccination) with commercially available therapeutics are permitted but must not be given within four weeks before or after the administration of the study drug.
Evaluations by visit:
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. 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 a missed infusion. Visit 7 has 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. Prior to infusion, a review of concomitant medications and AEs takes place. If the subject continues to be eligible for enrollment, the subject will be infused with study medication and will remain in the infusion clinic for at least 1 hour following the infusion for safety assessments on Visit 2 (Day 1), and 15 minutes for the subsequent visits.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a single center, open label, proof of concept, out-patient study.
| Arm | Type | Receives |
|---|---|---|
| infusion of IVIG | Experimental | Biological: Octagam 10% |
Who may qualify
- Ages
- 50 to 84 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Age 50 to <85 years.
- Evidence of amyloid pathology on Florbetapir PET at screening.
- Diagnosis of MCI due to AD based on NIA-AA criteria. (APPENDIX A)
- MRI brain (with past 24 months) which shows evidence of mild hippocampal atrophy and/or bilateral parietal atrophy.
- CDR score of 0.5
Key exclusion criteria (28 listed)
- Has significant neurological disease other than MCI that in the opinion of the investigator 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.
- History of screening visit brain MRI scan indicative of any other significant abnormality, including but not limited to multiple microhemorrhages (2 or more), history or evidence of a single prior hemorrhage > 1 cm3, multiple lacunar infarcts (2 or more) or evidence of a single prior infarct > 1 cm3, evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions of significance as determined by the PI (e.g., arachnoid cysts or brain tumors such as meningioma).
- Brain MRI shows moderate or severe cortical or hippocampal atrophy.
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 |
|---|---|---|
| Octagam 10%FDA approved human normal immunoglobulin solution ready for intravenous administration | Biological | infusion of IVIG |
Primary outcome
Change in Baseline Standard Uptake Ratio Values (SUVr) of Florbetapir PET at 3 Months
Time frame: Baseline to 3 months
Amyloid deposition in the brain is thought to lead to the development of cognitive decline and conversion to AD. Each participant's amyloid burden can also be quantified through the computation of a Standard Uptake Value ratio (SUVr).
Change in Baseline Retinal Amyloid Imaging (RAI) at 3 Months
Time frame: Baseline to 3 months
This is a noninvasive imaging technique that can detect amyloid-beta deposition in the retinas of the eye.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: 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.
- Individual participant dataSharing planned: No
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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, MD principal investigator
Sutter Health
Carol Parise, PhD study director
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 Octagam 10% 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 16 inclusion and 28 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 25 Jun 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. 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 16 Apr 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?
Change in Baseline Standard Uptake Ratio Values (SUVr) of Florbetapir PET at 3 Months (time frame: Baseline to 3 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?
On the ClinicalTrials.gov record for NCT03319810, which also lists 1 linked publication.
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 25 Jun 2019.