The objective of the study is to investigate the effect of alfa2-adrenoceptors on bone turnover.
ID
Source
Brief title
Condition
- Bone, calcium, magnesium and phosphorus metabolism disorders
- Bone disorders (excl congenital and fractures)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the change in serum concentrations of collagen type
1 cross-linked C-telopeptide (CTX) on the intervention and on the control day.
Secondary outcome
The secondary objective is the change in catecholamine levels and serum
concentration of another bone turnover marker, procollagen type I N propeptide
(P1NP) on the intervention day (clonidine 0.3mg) and on the control day (no
intervention).
We will also investigate whether osteoclasts are responsive to the
alpha2-adrenoceptor agonist clonidine in vitro, by measuring osteoclast
activity and formation.
Background summary
Osteoporosis is a common disease that is characterized by low bone mass with
microarchitectural disruption and skeletal fragility, resulting in increased
risk of fracture.
Recent research suggests that beta2-adrenoceptor is not the single receptor
involved in bone turnover regulation. In a mouse model of chronic elevated
sympathetic tone owing to double knockout of alpha2A/2C-adrenoceptors, mice
present a phenotype of high bone mass, with an increased formation and
decreased bone resorption. Further investigation of the specific functions of
the alpha2-adrenoceptors and their interaction in bone metabolism in humans
will be needed to enhance our understanding of the role of the SNS in the
skeleton, which certainly will contribute to novel strategies for the treatment
of osteoporosis.
Study objective
The objective of the study is to investigate the effect of alfa2-adrenoceptors
on bone turnover.
Study design
Open label randomized controlled cross-over trial and observational study.
Intervention
All participants will visit the AMC on three different occasions. On the first
two days subjects will receive either a single oral dose of clonidine 0.3mg or
no intervention. Participants will be randomized to either clonidine followed
by no intervention or no intervention followed by clondine. The first day will
be followed by a wash out period of 1 week. Two weeks after the second day
subjects will visit the AMC a third day for a single blood sample without
intervention.
Study burden and risks
During the intervention, participants will have to take a single dose of oral
clondine. Clonidine, an alpha2-adrenergic agonist, is widely prescribed in
patients with hypertension, menopausal flushing, as migraine prophylaxis and
during withdrawal from opiates. The most common side effects of clonidine
treatment are sedation, dry mouth, hypotension, fatigue and dizziness. Other
less common side effects are headache, diarrhea, obstipation, nausea, vomiting,
nervousness, bradycardia, insomnia, nightmares, confusion and hallucinations.
The latest being less likely considering patients will only receive a single
dose. Fasting blood samples will be drawn on the three days that patients visit
the AMC. The total volume of blood samples during the entire protocol will not
exceed 286 ml. Risks associated with venous blood sampling is also negligible.
Meibergdreef 9
Amsterdam Zuidoost 1105AZ
NL
Meibergdreef 9
Amsterdam Zuidoost 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Age: 18-70 years
Exclusion criteria
- Hypersensitivity to the active substrate or to any of the excipients
- Severe bradycardia, like sick sinus syndrome and a second or third degree atrioventricular block
- Use of antihypertensive drugs (including diuretics)
- Use of drugs with negative effects on heart rhythm
- Any medication or disease influencing bone turnover
- Inability to give informed consent
- RR < 110/70 mmHg at the start of the experiment
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-004634-41-NL |
| CCMO | NL42339.018.12 |
| OMON | NL-OMON23544 |