Plasma Hydrogen Sulfide as a Biomarker for Alzheimer's Disease and Related Dementias

Alzheimer Disease Clinical Trial

Official title:

Plasma Hydrogen Sulfide as a Biomarker for Alzheimer's Disease and Related Dementias

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05060848
• Other study ID #: 00000059
• Status: Active, not recruiting
• Start date: April 1, 2021
• Est. completion date: May 2027

Study information

• Verified date: March 2023
• Source: Louisiana State University Health Sciences Center Shreveport
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Hydrogen sulfide is a signaling molecule that is important for vascular health. Because vascular factors such as hypertension and high cholesterol are risk factors for Alzheimer's disease and related dementias, we hypothesize that hydrogen sulfide plays an important role in brain health as well. We will compare blood levels of hydrogen sulfide across groups of people with and without dementia. We will also look at the relationship between hydrogen sulfide, cognitive dysfunction and measures of brain microvascular disease examine the contribution of hydrogen sulfide to cognitive decline. Our goal is to identify a biomarker of vascular dysfunction in dementia.

Description:

We have described hydrogen sulfide (H2S), a signaling molecule important in vascular homeostasis, as a biomarker of cardiovascular disease. There is accumulating evidence that vascular factors such as hypertension, hypercholesterolemia, and type 2 diabetes are associated with increased risk of Alzheimer's disease and related dementias (ADRD). Furthermore, in the brain, H2S acts as a neurotransmitter/second messenger produced following nerve excitation. It also modulates N-methyl-D-aspartate (NMDA) receptors during long term potentiation for memory consolidation. Three biochemical forms of reactive sulfur pools exist: free H2S, acid-labile (e.g. iron-sulfur clusters) and bound sulfide (e.g. persulfides, polysulfides). We hypothesize that H2S becomes dysregulated in ADRD, where vascular and cognitive functions are linked. We will use analytical biochemical methods to measure plasma H2S and its metabolites, and 3T MRI to evaluate indicators of microvascular disease in ADRD. We will compare H2S levels in people with and without cognitive dysfunction consistent with ADRD, and determine the specificity and sensitivity of H2S indistinguishing people with and without cognitive dysfunction. In addition, because previous studies report differences in the incidence and prevalence of ADRD by race and sex, we will compare outcomes across these groups as well. Finally, we will examine the potentially mediating role of H2S in the relationship between cognitive function and microvascular disease.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: May 2027
• Est. primary completion date: May 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years to 100 Years

Eligibility

Inclusion Criteria:

• All participants must be aged >55 years with English as the 1° language, with stable permitted medications for <4 weeks, geriatric depression scale score <6, visual and auditory acuity adequate to perform tests, and history of education excluding developmental cognitive abnormalities.

Exclusion Criteria:

• Exclusion criteria are history of significant neurologic disease or mental illness, unstable medical conditions that could interfere with completion of study, substance abuse within 2 years, contraindications to MRI, abnormal findings on MRI, history of chronic kidney disease, and investigational agents within 1 month of participation.

Related Conditions & MeSH terms

• Alzheimer Disease
• Dementia

Locations

Country	Name	City	State
United States	LSU Health Shreveport Center for Brain Health	Shreveport	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Louisiana State University Health Sciences Center Shreveport

Country where clinical trial is conducted

United States, 

References & Publications (1)

Disbrow E, Stokes KY, Ledbetter C, Patterson J, Kelley R, Pardue S, Reekes T, Larmeu L, Batra V, Yuan S, Cvek U, Trutschl M, Kilgore P, Alexander JS, Kevil CG. Plasma hydrogen sulfide: A biomarker of Alzheimer's disease and related dementias. Alzheimers D — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Comorbidity Data (covariates)	BP, weight, Hx of smoking, diabetes, hypertension, elevated cholesterol	Prospective, single measurement
Primary	Cognitive Outcomes	ADAS Cog score	Prospective, single measurement
Primary	Imaging Outcomes	MRI based brain volume measures, FLAIR lesion volume	Prospective, single measurement
Primary	Blood Outcomes	Plasma Hydrogen sulfide including metabolites: free, acid labile, bound and total sulfides.	Prospective, single measurement
Secondary	Demographic Data	Age, Race, Sex, Socioeconomic status	Prospective, single measurement