Bioavailability, Gut Microbiome, Safety
Conditions
Brief summary
To test how two weeks of curcumin supplementation would cross the blood brain barrier (BBB) and attach to amyloid beta proteins, to assess the feasibility (safety and bioavailability), and to explore the resulting abundance/composition of gut microbiota.
Detailed description
Alzheimer's disease (AD) leads to progressive cognitive decline. Increased amyloid beta (Aβ) burden and Aβ deposits have been shown in the AD retina. Aβ accumulation inside retinal pericytes in AD and pericyte degeneration in the retina mirror prominent features of brain AD pathology. Curcumin, a derivative of turmeric, has a high affinity for amyloid beta. Thus, curcumin would bind to amyloid beta plaques and emit a strong fluorescent signal, suggesting it can be a powerful diagnostic tool for AD. Emerging evidence has shown the connection between the brain and GI tract (gut microbiome), and its potential implications for both metabolic and neurologic diseases including AD. This pilot study is to test how two weeks of curcumin supplementation would cross the blood brain barrier and attach to amyloid beta proteins and to explore the resulting abundance/composition of gut microbiota. The investigators plan to recruit subjects through direct person-to-person solicitation in the Ophthalmology clinics, health fairs, community events, flyers, non-solicited email system, campus announcements, Clinical Research Institute Volunteer Database website, local radio, newspapers, senior newsletters, and TV scripts. The Clinical Research Institute Volunteer database will also be queried and potential subjects contacted as requested in their form. The investigators plan to enroll approximately 100-150 patients to obtain 30-40 qualified subjects at the start of the study. After screening, qualified participants will be randomly assigned to a low curcumin group or high curcumin group. Thus, this pilot study would focus on characterizing the distribution, manifestation, and prevalence of curcumin-loaded retinal Aβ deposits in study subjects with existing Aβ plaque (primary outcome). In addition, this study will assess safety, bioavailability, and fecal microbiome composition (secondary outcome). All outcomes will be assessed at baseline and after 2 weeks of intervention. Data will be analyzed statistically.
Interventions
DRUGLow curcumin group
One curcumin capsule (250 mg curcumin) after each meal, 3 times a day for 2 weeks.
DRUGHigh curcumin group
One curcumin capsule (500 mg curcumin) after each meal, 3 times a day for 2 weeks.
Sponsors
Texas Tech University Health Sciences Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
This is a 2-week double blinded, placebo-controlled, and randomized intervention trial with allocation 1:1 for two treatment arms (low curcumin group and high curcumin group).
Eligibility
Sex/Gender
ALL
Age
40 Years to 89 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion: * Both male and female, age 40 - 89 years. * Diagnosed with Aβ deposits in retina (peripheral superior quadrants)--to be confirmed after consent obtained. If there is documentation the potential participant has been diagnosed with Aβ deposits in retina within 6 months before the consent session, we will use this diagnosis/documentation for eligibility criteria. Otherwise, the ophthalmic exam will be repeated after consent is obtained for the study. * No pre-existing liver or kidney diseases by self-report. Exclusion: * Patients with ocular diseases (macular degeneration, severe diabetes retinopathy) * Had used systemic antibiotics within 1 month prior to the start of the study intervention * Had taken any turmeric or curcumin products within 2 weeks prior to the start of the study intervention * Had a known allergy to black pepper * Women that are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retinal imaging- amyloid fluorescent intensity | Baseline | To access amyloid fluorescent intensity |
| Retinal imaging-amyloid fluorescent deposit number | Baseline | To access amyloid fluorescent deposit number |
| Retinal imaging-amyloid fluorescent location | Baseline | To access amyloid fluorescent location |
| Retinal imaging-amyloid fluorescent intensity | After 2 weeks | To access amyloid fluorescent intensity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Liver function-serum ALT | Baseline | To assess serum ALT |
| Kidney function-serum BUN | Baseline | To assess serum BUN |
| Bioavailability- curcumin concentrations in plasma | Baseline | To measure curcumin concentrations in plasma |
| Gut microbiome-composition | Baseline | To measure the composition of intestinal bacterial in feces |
| Gut microbiome-abundance | Baseline | To measure the abundance of intestinal bacterial in feces |
| Bioavailability-curcumin concentrations in red blood cells | Baseline | To measure curcumin concentrations in red blood cells |
| Bioavailability-curcumin concentrations in plasma | After 2 weeks | To measure curcumin concentrations in plasma |
| Liver function-serum AST | Baseline | To assess serum AST |
Countries
United States
Contacts
Primary ContactChwan-Li (Leslie) Shen, PhD
Outcome results
None listed