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): 5
• 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 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
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• bodyweight ≥ 12 kg
• native (not surgically replaced) ascending aorta
• diagnosed with SMDS with confirmed ACTA2 mutation disrupting arginine 179
• females with negative urine pregnancy test
• must agree to use acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study

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.
• Inability to tolerate PET/CT imaging and echocardiography without sedation.
• 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	Time Frame
Change in Fluoro-18-Deoxyglucose (18F-FDG ) uptake in aortic wall as measured by positron emission tomography (PET)/computerized tomography (CT) imaging	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
Change in aortic measurements as assessed by echocardiography	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: David Murdock, MD, 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, 2025
• Study Completion (Estimated): July 25, 2025

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 (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

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: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease; Syndrome; Cerebrovascular Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• 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