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

NCT06280482 | Recruiting Phase 1 FDA Drug

• 1 other identifier: HSC-MS-23-0332
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Smooth Muscle Dysfunction Syndrome (SMDS)

Keywords

smooth muscle aortic alpha-actin (ACTA2); arginine 179 residue; Nicotinamide Riboside; Stroke; Cerebrovascular Disease; Thoracic Aortic Aneurysms and Dissections

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (5)

• 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)

Study Arms (1)

Treatment

EXPERIMENTAL

Drug: Nicotinamide riboside (NR)

Interventions

Nicotinamide riboside (NR) DRUG

Participants will take their weight-based dose of NR once daily by mouth with food for 60 days.

Treatment

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals diagnosed with SMDS with confirmed ACTA2 mutation disrupting arginine 179
• Parental/guardian permission (informed consent) and, if appropriate, child assent.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Stroke; Cerebrovascular Disorders; Aortic Aneurysm, Thoracic

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Aortic Aneurysm; Aneurysm; Aortic Diseases

Study Officials

• Dianna Milewicz, MD, PhD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dianna M Milewicz, MD, PhD

CONTACT

(713) 500-6725; Dianna.M.Milewicz@uth.tmc.edu

David R Murdock, MD

CONTACT

(713) 500-6735; David.R.Murdock@uth.tmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 19, 2024
• First Posted: February 28, 2024
• Study Start: March 6, 2024
• Primary Completion (Estimated): July 25, 2027
• Study Completion (Estimated): July 25, 2027
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)