Nicotinamide Riboside (NR) to Treat Moyamoya-like Cerebrovascular Disease in Smooth Muscle Dysfunction Syndrome (SMDS)

Phase 1RecruitingNCT06280482

The University of Texas Health Science Center, Houston15 enrolled

Overview

The purpose of this study is to determine whether SMDS patients treated with NR at the proposed dose exhibit decreased glucose uptake in the aorta, to determine if NR treatment results in measurable changes of blood NAD+ and NR levels, to determine if aortic measurements are stable after treatment with NR and to evaluate the safety and tolerability of NR in SMDS patients.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Smooth Muscle Dysfunction Syndrome (SMDS)

Interventions

Nicotinamide riboside (NR)DRUG

Eligibility

Sex: ALLMin age: 1 Year

Medical Language ↔ Plain English

Inclusion Criteria: * Individuals diagnosed with SMDS with confirmed ACTA2 mutation disrupting arginine 179 * Parental/guardian permission (informed consent) and, if appropriate, child assent. Exclusion Criteria: * Individuals who have undergone surgery to replace aneurysmal or dissected ascending and root aortic tissue with a graft. * Additional medical conditions that impair the patient's ability to participate in the study. * Known allergy or sensitivity to niacin or nicotinamide riboside. * Prior consumption of niacin or nicotinamide riboside supplement within the prior eight weeks. * Failure to provide informed consent. * Concurrent participation in another intervention trial.

Outcomes

Primary Outcomes

Change in systolic blood

Time frame: Baseline , 8 weeks

Change in cerebral oxygenation and perfusion as assessed by the Head-up tilt table testing (HUTT) with near-infrared spectroscopy (NIRS) monitoring.

Time frame: Baseline , 8 weeks

Change in cognitive function as assessed by the NIH Toolbox assessment

NIH Toolbox assessment evaluates multiple domains of cognitive performance including executive function, attention, episodic memory, language, processing speed, and working memory. Individual test scores are combined into a composite cognition score and reported as age-adjusted T-scores (mean = 50, SD = 10), where higher scores indicate better cognitive function.

Time frame: Baseline , 8 weeks

Change in autonomic symptoms as assessed by the Composite Autonomic Symptom Score 31 (COMPASS-31) survey

This is a 31 item questionnaire and each is scored from 0 (no symptoms) to 100(maximum symptom burden), with higher scores indicating more severe autonomic dysfunction.

Time frame: Baseline , 8 weeks

Change in Impact of headaches as assessed by the Headache Impact Test (HIT-6) questionnaire

HIT-6 questionnaire consists of 6 questions, each scored from 6(never) to 13(always), with total scores ranging from 36 to 78. Higher scores indicate a greater impact of headaches on quality of life.

Time frame: Baseline, 8 weeks

Pulmonary function tests (PFTs), including spirometry and lung volume measurements

Time frame: Baseline, 8 weeks

Change in Aortic diameter as assessed by the echocardiography

Time frame: Baseline , 8 weeks

Secondary Outcomes

Change in Levels of Nicotinamide adenine dinucleotide (NAD+) in whole blood as measured by high-performance liquid chromatography (HPLC)

Time frame: Baseline , 8 weeks

Change in Levels of NR in whole blood as measured by high-performance liquid chromatography (HPLC)

Time frame: Baseline , 8 weeks

Safety as assessed by number of participants that show drug toxicity as shown in bloodwork

Time frame: Baseline

Safety as assessed by number of participants that show drug toxicity as shown in bloodwork

Time frame: end of study (8 weeks after baseline)

Tolerability as assessed by the number of patients who complete study

Time frame: end of study( 8 weeks after baseline)

Nicotinamide Riboside (NR) to Treat Moyamoya-like Cerebrovascular Disease in Smooth Muscle Dysfunction Syndrome (SMDS)

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts