Clinical trial NCT06280482: Nicotinamide Riboside (NR) to Treat Moyamoya-like Cerebrovascular Disease in Smooth Muscle Dysfunction Syndrome (SMDS)
Official title: Nicotinamide Riboside (NR) to Treat Moyamoya-like Cerebrovascular Disease in Smooth Muscle Dysfunction Syndrome (SMDS)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
First posted: 2024-02-28
Enrollment: 5
Sex: ALL
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in Fluoro-18-Deoxyglucose (18F-FDG ) uptake in aortic wall as measured by positron emission tomography (PET)/computerized tomography (CT) imaging
timeFrame: Baseline , 8 weeks
Secondary outcomes:
measure: Change in Levels of Nicotinamide adenine dinucleotide (NAD+) in whole blood as measured by high-performance liquid chromatography (HPLC)
timeFrame: Baseline , 8 weeks
measure: Change in Levels of NR in whole blood as measured by high-performance liquid chromatography (HPLC)
timeFrame: Baseline , 8 weeks
measure: Change in aortic measurements as assessed by echocardiography
timeFrame: Baseline , 8 weeks
measure: Safety as assessed by number of participants that show drug toxicity as shown in bloodwork
timeFrame: Baseline
measure: Safety as assessed by number of participants that show drug toxicity as shown in bloodwork
timeFrame: end of study (8 weeks after baseline)
measure: Tolerability as assessed by the number of patients who complete study
timeFrame: end of study( 8 weeks after baseline)
Other outcomes:
Locations:
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: David Murdock, MD
role: PRINCIPAL_INVESTIGATOR
References: