To investigate the effect of daily intake of 350 milligrams of magnesium citrate oral supplementation over a period of six months on calciprotein particle maturation time (T50) in serum, a measure of calcification propensity, and on vascular…
ID
Source
Brief title
Condition
- Diabetic complications
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoints are serum T50 and carotid-femoral pulse wave velocity (c-f
PWV) at three and six months after baseline.
Secondary outcome
Secondary endpoints are total magnesium, sodium, potassium, calcium, phosphate,
urea, total protein, creatinine, triglycerides, total cholesterol,
LDL-cholesterol, HDL-cholesterol, fasting plasma glucose and HbA1C
concentrations at three and six months after baseline.
Background summary
Despite therapeutic strategies targeting multiple cardiovascular risk factors,
cardiovascular disease (CVD) remains the leading cause of morbidity and
mortality in people with type 2 diabetes (T2D). Medial arterial calcification
(MAC) is a particular form of calcification that occurs through mineralization
of the elastin fibers and precipitation of calcium phosphate in the tunica
media, in the absence of lipids. It occurs in approximately 35% of people with
T2D and represents an alternative pathophysiological mechanism leading to
adverse cardiovascular events than atherosclerosis. It is hypothesized that
increased serum calcification propensity leads to MAC and increased vascular
stiffness, followed by increased risk of left ventricular hypertrophy and heart
failure . While lipoprotein lowering treatment is used to reduce intimal
calcification, there is currently no treatment that specifically targets MAC.
The propensity of serum to calcify can be measured using the maturation time of
calciprotein particles in serum (T50 test). A shorter T50 has been associated
with higher presence of MAC in people with chronic kidney disease and with
all-cause and cardiovascular mortality in the general population.
Magnesium is shown to reduce MAC progression in animal models and in people
with kidney disease. Oral magnesium supplementation also improved vascular
stiffness and cardiac function in people with CVD.
Accordingly, magnesium supplementation could be an effective strategy to tackle
MAC by reducing vascular stiffness and serum calcification propensity in people
with T2D.
Study objective
To investigate the effect of daily intake of 350 milligrams of magnesium
citrate oral supplementation over a period of six months on calciprotein
particle maturation time (T50) in serum, a measure of calcification propensity,
and on vascular stiffness, in people with T2D.
Study design
A monocenter double-blind, randomized, placebo-controlled parallel trial.
Intervention
Magnesium citrate, 350 mg daily orally for six months, versus placebo.
Study burden and risks
The study involves a total of four visits over a period of six months. Overall,
the visits will take approximately 1.5 hours* time. Oral magnesium citrate
supplements or placebo supplements have to be taken daily for 6 months. Oral
magnesium citrate supplements have a good safety profile and previous studies
reported a low rate of adverse events (mainly gastrointestinal such as
diarrhea, nausea, and vomiting) that usually only occur when used in very large
doses. At screening and at the first follow-up after three months, participants
will undergo a blood sampling for plasma magnesium concentrations and
measurement of c-f PWV. At baseline and at the second follow-up after six
months, participants will undergo blood sampling for magnesium as well as other
biomarkers, will hand in a 24-hour urine collection and will undergo
measurements of c-f PWV. Additionally, dietary intake of magnesium will be
assessed by a short food frequency questionnaire - the Dutch Healthy Diet index
Food Frequency Questionnaire - at baseline and the second follow-up after six
months. Vena puncture may cause discomfort and may result in bruising that
continues up to a few days after the examinations. Determination of c-f PWV is
a non-invasive procedure method that measures the propagation of the forward
pressure wave traveling along the aorta. Participants gain no individual
benefit from their participation in the study. However, the study is expected
to increase our understanding of MAC as a mechanism for increased CVD risk in
T2D, and may ultimately lead to a new therapeutic intervention.*
De Boelelaan 1089a
Amsterdam 1081HV
NL
De Boelelaan 1089a
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
age 50-80 years;
Diabetes Mellitus Type 2;
Presence of a predominantly medial arterial calcification pattern on a
previously conducted CT scan of the legs;
Carotid-femoral pulse wave velocity higher than 12 meter per seconde;
Ability to provide informed consent prior to initiating screening visit
procedures.
Exclusion criteria
Myasthenia Gravis;
Use of medications that might interact with magnesium supplements
(levothyroxine, osteoporosis medications tiludronate and alendronate, warfarin);
Advanced diabetes complications (proliferative retinopathy, disabling
polyneuropathy, nephropathy with an estimated glomerular filtration rate
(eGFR), calculated with the Jaffé method according to the Chronic Kidney
Disease Epidemiology Collaboration equation <15 mL/min/1.73m2 or chronic
dialysis, cardiac complications);
Uncontrolled hyperthyroidism or active parathyroid disease;
Chronic diarrheal disease or inflammatory bowel diseases;
Congestive heart failure, bradycardia with a resting heart rate below 60 and
systolic blood pressure less than 90 mmHg;
Atrial Fibrillation;
Previous aortic surgery;
Severe hepatic insufficiency;
Malignancy or other non-cardiac conditions limiting life expectancy to <3 years;
Using food supplements that contain magnesium, or unwilling to stop two weeks
before randomization;
Mental or legal incapacitation to provide informed consent;
Plasma magnesium concentration*>*2.6*mg/dL or < 1.5 mg/dL at screening.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ISRCTN | ISRCTNsubmissionreference41701(nognietgepubliceerd,wordtaangepast) |
| CCMO | NL81281.029.22 |