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

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 Overview

• Status: Recruiting
• Conditions: Smooth Muscle Dysfunction Syndrome (SMDS)
• Intervention / Treatment: Drug: Nicotinamide riboside (NR)

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: David R Murdock, MD; Phone Number: (713) 500-6735; Email: David.R.Murdock@uth.tmc.edu
• Study Contact Backup: Name: Dianna M Milewicz, MD, PhD; Phone Number: (713) 500-6725; Email: Dianna.M.Milewicz@uth.tmc.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas Health Science Center at Houston
      • Contact: Dianna Milewicz, MD, PhD; Phone Number: 713-500-6725; Email: Dianna.M.Milewicz@uth.tmc.edu
      • Contact: David Murdock, MD; Phone Number: (713) 500-6735; Email: David.R.Murdock@uth.tmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment	Drug: Nicotinamide riboside (NR); Participants will take their weight-based dose of NR once daily by mouth with food for 60 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in systolic blood		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.		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.	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.	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.	Baseline, 8 weeks
Pulmonary function tests (PFTs), including spirometry and lung volume measurements		Baseline, 8 weeks
Change in Aortic diameter as assessed by the echocardiography		Baseline , 8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Levels of Nicotinamide adenine dinucleotide (NAD+) in whole blood as measured by high-performance liquid chromatography (HPLC)	Baseline , 8 weeks
Change in Levels of NR in whole blood as measured by high-performance liquid chromatography (HPLC)	Baseline , 8 weeks
Safety as assessed by number of participants that show drug toxicity as shown in bloodwork	Baseline
Safety as assessed by number of participants that show drug toxicity as shown in bloodwork	end of study (8 weeks after baseline)
Tolerability as assessed by the number of patients who complete study	end of study( 8 weeks after baseline)

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: Dianna Milewicz, MD, PhD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2024
• Primary Completion (Estimated): July 25, 2027
• Study Completion (Estimated): July 25, 2027

Study Registration Dates

• First Submitted: February 19, 2024
• First Submitted That Met QC Criteria: February 19, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 5, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Stroke; Nicotinamide Riboside; Cerebrovascular Disease; smooth muscle aortic alpha-actin (ACTA2); arginine 179 residue; Thoracic Aortic Aneurysms and Dissections
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Aortic Diseases; Aneurysm; Aortic Aneurysm; Stroke; Cerebrovascular Disorders; Aortic Aneurysm, Thoracic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; nicotinamide-beta-riboside
• Other Study ID Numbers: HSC-MS-23-0332

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No