In this study, the highest acceptable dose of an amino acid called citrulline will be established in people who have a mitochondrial disorder. Previous research conducted by several groups including our center at Baylor College of Medicine has determined that there is a deficiency of a compound called nitric oxide in people affected with MELAS.

MELAS Syndrome

To determine the safest maximum dose of L-Citrulline which could be used as a potential treatment for adults with disorder of energy metabolism called MELAS

L-Citrulline

L-citrulline and Metformin in Duchenne's Muscular Dystrophy

Baylor St. Luke'S Medical Center

L-Citrulline Dose Finding Safety Study in MELAS

Phase-1, Dose Finding and Safety Study on L- Citrulline Treatment of Nitric Oxide Deficiency in MELAS

Measurement of the incidence of treatment-emergent adverse events in a safety and tolerability phase 1 study.
The following Dose Limiting
Toxicities (DLTs) will be measured:
Treatment‐related adverse events (AE) at grade 3 or higher, or worsening of baseline status, defined by increase of at least 2 grades, if baseline grade is ≤1. The AEs will be graded based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. Subjects will be specifically monitored for the occurrence of the following adverse events:
Syncope
Dizziness
Blurred Vision
Fatigue
Concentration Impairment
Nausea
Vomiting
Diarrhea
Hypoglycemia
Headache
Orthostatic hypotension defined as a decrease in systolic blood pressure of 20 mm Hg, or a decrease in diastolic blood pressure of 10 mm Hg, within three minutes of standing when compared with blood pressure from the sitting or supine position.

Changes in cerebral blood flow by using arterial spin‐labeling (ASL) magnetic resonance imaging (MRI) will be measured in milliliters per 100 grams of tissue per minute at four weeks while on citrulline and compared to measurement at baseline in milliliters per 100 grams of tissue per minute before the use of citrulline

Changes in cerebrovascular reactivity by using arterial spin‐labeling (ASL) magnetic resonance imaging (MRI) will be measured in milliliters per 100 grams of tissue per minute at four weeks while on citrulline and compared to measurement in milliliters per 100 grams of tissue per minute at baseline before use of citrulline

Concentrations of plasma citrulline, arginine, ornithine, and alanine will be measured at baseline before citrulline supplementation and at four weeks during citrulline supplementation to determine the changes in concentration in micromoles per liter

Concentrations of plasma lactate and plasma alanine will be measured at baseline before citrulline supplementation and at four weeks during citrulline supplementation to determine the change in concentration in micromoles per liter in plasma alanine and in millimoles per liter in plasma lactate

Concentration of plasma guanidino compounds will be measured at baseline before citrulline supplementation and at one week during citrulline supplementation by using untargeted metabolomics profiling and values will be expressed in Z scores

Fernando Scaglia

Professor

Baylor College of Medicine

National Institutes of Health (NIH)

University of South Florida

Columbia University

In this intervention period children will receive a vascular ready-to-use supplementary food with added L-Arginine & L-Citrulline plus daily chloroquine

In this intervention period children will receive a regular ready-to-use supplementary food plus weekly dose of chloroquine

Sickle Cell Disease

Daily vascular ready-to-use supplementary food containing protein, energy and fortified with 1 x recommended daily allowance(RDA) of vitamins and minerals except for folic acid = 1mg and with no iron fortificant included and fortified with arginine and citrulline amino acids

Vascular ready-to-use supplementary food

Daily ready-to-use supplementary food containing protein, energy and fortified with 1 x RDA vitamins and minerals except for folic acid = 1mg and with no iron fortificant included.

Regular Ready-to-use supplementary food

Chloroquine

Muhimbili University of Heath and Allied Sciences (MUHAS)

Vascular Function Intervention Trial in Sickle Cell Disease

Development of a Ready-to-use Nutraceutical Food for Patients With Sickle Cell Disease (SCD): Testing of Vascular Support Components

We will compare the effects of the RUSFv compared to the simple RUSF on:
The ratio of plasma arginine to ornithine & ratio of arginine to ADMA and adjust for values at baseline
Time frame definition:
0 months = baseline
4 months = after 1st four-month intervention period, before washout 1
8 months = after 1st 4 month washout period before 2nd intervention period
12 months = after 2nd four-month intervention period, before washout 2
16 months = after 2nd 4 month washout period (study end)

Comparison of the effects of the RUSFv to the simple RUSF on vascular function, assessed using flow mediated dilatation (FMDmax), adjusted for baseline values at time 0. Values will also be determined at time point at month 8, in order to check for possible carry-over effect.

We will compare the effects of RUSF compared to no RUSF on rates of growth by comparison of the 2 intervention periods combined with the two washout periods combined, by conducting measurements at months 0, 4, 8, 12 & 16.

Full blood counts (FBC) of ethylenediaminetetraacetic acid (EDTA) whole blood will be conducted

Concentrations of soluble adhesion molecules (VCAM-1, vascular endothelial growth factor-1 (VEGF-1), tumor necrosis factor-alpha (TNF-α) & e-selectin, tissue factor and IL-6) will be measured in frozen (-80⁰C) plasma aliquots.
C-reactive protein concentrations will be measured in frozen serum samples and leukocyte counts from FBC.

Plasma haemoglobin will be measured in frozen serum aliquots. Unconjugated bilirubin and lactate dehydrogenase in fresh serum.

Study personnel will administer detailed questionnaires at weekly home visits to assess the frequency of all sickle and non-sickle associated morbidity and health seeking behaviour, with a focus on painful episodes. Participatory research will be used to determine the likely application and optimal formatting of pain diaries to be completed by patients and families in addition to the standard questionnaire.

aspartate transaminase, alkaline phosphatase, total and direct bilirubin and creatinine will be measured in fresh serum

glomerular filtration rate will be estimated using an adaptation of the Schwartz equation in which muscle mass measured using bioimpedance will be included in the formula instead of the usual estimate. The outcome will be adjusted for values at baseline.

London School of Hygiene and Tropical Medicine

Wellcome Trust

Oral L-arginine supplementation will be administered to subjects with MELAS for 48 hours at a dose of 10 grams per M2 per day. Arginine will be given every 4 hours.

Oral L-citrulline supplementation will be administered to subjects with MELAS for 48 hours at a dose of 10 grams per M2 per day. Citrulline will be given every 4 hours

Arginine or citrulline will be given orally at dose of 10 grams per meter square body surface area per day divided every 4 hours.

citrulline/udar mózgu

L-Citrulline Dose Finding Safety Study in MELAS

Vascular Function Intervention Trial in Sickle Cell Disease

Nitric Oxide Production in MELAS Syndrome

Najbardziej kompletna baza danych ziół leczniczych poparta naukowo