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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01AG068062-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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In this research study the investigators want to find out if a non-invasive electrical brain stimulation method called RAVANS (also called tVNS) can have a beneficial effect on cognition in older individuals. The investigators also want to understand whether certain individual factors contribute to the effect of RAVANS on cognition. RAVANS is only used in research studies.
The intervention will be studied in 140 older individuals using a randomized cross-over design of sham versus RAVANS stimulation (2 sessions separated by 4 weeks) during a functional magnetic resonance imaging (fMRI) task. Participants will then be randomized to daily tVNS or sham sessions during 10 visits within two weeks, and two follow-up cognitive assessments each after 2 months of the last intervention session. The face-name association task will be the main outcome measure. The investigators will also draw blood twice to examine whether the response on the outcome is dependent on Alzheimer's disease related biomarker, and whether RAVANS has effects on inflammatory responses.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sham preceded by cross-over Sham-Stimulation | Sham Comparator | Cross-over: Sham followed by experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) Wash-out period of four weeks Ten daily sessions of sham during 2 weeks |
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| Sham preceded by cross-over Stimulation-Sham | Sham Comparator | Cross-over: experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) followed by Sham Wash-out period of four weeks Ten daily sessions of sham during 2 weeks |
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| Stimulation preceded by cross-over Sham-Stimulation | Experimental | Cross-over: Sham followed by experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) Wash-out period of four weeks Ten daily sessions of RAVANS during 2 weeks |
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| Stimulation preceded by cross-over Stimulation-Sham | Experimental | Cross-over: experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) followed by sham Wash-out period of four weeks Ten daily sessions of RAVANS during 2 weeks |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Active transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions | Other | Stimulation of vagus nerve in the outer ear |
| Measure | Description | Time Frame |
|---|---|---|
| Performance on the Face-name association memory task (FNAME) | Change from baseline at each visit where FNAME is completed: Scores are z-scores with a mean of zero. Higher scores are better (there is no minimum/maximum). | Up to 25 weeks: assessed during week 1, week 2, week 8,week 9, week 17 and week 25 |
| Being a responder as determined by Face-name association memory task (FNAME) change scores | Participants are grouped in being a responder (1) or non-responder (0). | Based on data from the first 4 weeks (cross-over) |
| Measure | Description | Time Frame |
|---|---|---|
| Performance on other cognitive composite scores: this includes a composite score of memory, a composite score of executive function and the Preclinical Alzheimer's disease cognitive composite. | Change from baseline at each visit where neuropsychological data is collected. Composites are calculated following a confirmatory factor analyses. All scores (correct answers) will be expressed in z-scores and higher scores are better (there is no minimum/maximum). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Heidi IL Jacobs, PhD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Charlestown | Massachusetts | 02129 | United States |
Consistent with NIH regulations, as provided in the manual of the NIH (SF424 (R&R)), data will be made available at the time of publication of the primary results or within 9 months of database lock, whichever comes first. A more detailed plan for sharing data and a data user agreement procedure will be set up during the study.
Consistent with NIH regulations, as provided in the manual of the NIH (SF424 (R&R)), data will be made available at the time of publication of the primary results or within 9 months of database lock, whichever comes first, and will be available for at least 3 years or until the sharing platform is no longer available. A more detailed plan for sharing data and a data user agreement procedure will be set up during the study.
Access to the clinical trial IPD can be requested by qualified scientists affiliated a research institutions, and will be provided following review and approval of a research proposal, statistical analysis plan and after signing a data user agreement. Requests can be submitted to wallestudy@mgh.harvard.edu from the first publication date of the primary results or within 9 months of database lock, whichever comes first. In the future, more information on data requests can be found on http://www.heidijacobs.org/. A more detailed plan for sharing data and a data user agreement procedure will be set up during the study.
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Randomized cross-over followed by placebo-controlled study (allocation to placebo or control condition takes APOE-E4 status into account and the previous ordering of the cross-over design)
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Participant will not be informed of condition. The investigators will work with blinded data (but can know the condition during intervention)
| cross-over Stimulation-Sham | Other | Cross-over: experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) followed by sham One time RAVANS versus one time Sham Two weeks wash-out |
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| cross-over Sham-Stimulation | Other | Cross-over: Sham followed by experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) One time RAVANS versus one time Sham Two weeks wash-out |
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| Sham transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions | Other | Sham stimulation of vagus nerve in the outer ear |
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| Up to 25 weeks: assessed during week 1, week 2, week 8,week 9, week 17 and week 25 |
| Change in inflammatory responses (aggregated) | Change from baseline to after intervention, these markers will be analyzed from blood:
Following stability analyses, specific markers will be selected (with advise by Dr. Arnold) and analysed individually (see outcome measures 5-10) and in aggregated form (here). Markers will be combined following a principal component analyses and will be normalised. Values will be expressed in z-scores. | Assessed during the first week and during week 9 |
| Change in inflammatory responses (interleukins) | Change from baseline to after intervention: - Interleukins (IL): IL-1β, IL-2, IL-6, IL-8 (expressed in IU, international units) | Assessed during the first week and during week 9 |
| Change in inflammatory responses (TNF) | Change from baseline to after intervention: - Tumor necreose factor alpha (TNF-α) (units/ml) | Assessed during the first week and during week 9 |
| Change in inflammatory responses (MIP) | Change from baseline to after intervention: - Macrophage inflammatory protein (MIP1B) (units/ml) | Assessed during the first week and during week 9 |
| Change in inflammatory responses (MCP) | Change from baseline to after intervention: -Monocyte chemoattractant protein (MCP-1) (units/ml) | Assessed during the first week and during week 9 |
| Change in inflammatory responses (C) | Change from baseline to after intervention: - Complement components: C1q and C3 (units/ml) | Assessed during the first week and during week 9 |
| Change in inflammatory responses (TREM) | Change from baseline to after intervention: - soluble triggering receptor expressed on myeloid cells (sTREM2) (units/ml) | Assessed during the first week and during week 9 |