The objective of the study is to study the effect of Teripratide (rhPTH 1-34) on undercarboxylated osteocalcin levels, testosterone concentrations, glucose tolerance and insulin sensitivity in male subjects with primary osteoporosis.
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Bone disorders (excl congenital and fractures)
- Gonadotrophin and sex hormone changes
Synonym
Research involving
Sponsors and support
Intervention
No registrations found.
Outcome measures
Primary outcome
* undercarboxylated osteocalcin
* testosterone concentrations
* insulin sensitivity determined by a hyperinsulinemic euglycemic clamp
Secondary outcome
NA
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. Normally, bone quality is maintained by a dynamic process,
known as bone remodeling.
Animal research shows that osteocalcin, secreted by osteoblasts, acts as a
hormone and influences the male gonal axis and insuline sensitivity. However no
randomized study in humans to evaluate the relationship between
undercarboxylated osteocalcin, the gonadal axis and insulin sensitivity has
been performed to date.
Study objective
The objective of the study is to study the effect of Teripratide (rhPTH 1-34)
on undercarboxylated osteocalcin levels, testosterone concentrations, glucose
tolerance and insulin sensitivity in male subjects with primary osteoporosis.
Study design
Open label randomized controlled cross-over trial
Intervention
The participants will be randomized to two treatment groups, in a cross-over
design.
Group 1 will first receive subcutaneous Teriparatide 20*g daily (12 weeks) and
then no treatment
Group 2 will first receive no treatment (12 weeks) and then subcutaneous
Teriparatide 20*g daily (12 weeks)
Study burden and risks
During the intervention, participants will receive a subcutaneous injection
daily. This injection will only cause minor discomfort.
The most common side effect of Teriparatide treatment is leg cramps and pain
(>10%). Other less common side effects (1-10%) are dizziness, nausea, vomiting,
gastroesophageal reflux, chest pain, hypotension, headache, muscle weakness and
depression. Teriparatide is registered for the treatment of osteoporosis for a
maximal duration of 24 months, whereas our subjects will only use it for 12
weeks. When the study ends all patients will continue with bisphosponate
treatment. Both anabolic and antiresorptive agents are approved for the
treatment of osteoporosis. But since it is only reimbursed in certain cases,
Teriparatide is not used as standard therapy for the treatment or prevention of
osteoporosis.
There are several reasons why we choose this study design. All patients
included in the study have a treatment indication But patients are only
deprived of medication for a total of 12 weeks. We however feel that we do not
expose the study subjects to an unacceptable risk of fractures by depriving
them of medication for a total of 12 weeks based on the ten-year probability of
a major osteoporotic fracture and relative risk reduction achieved with
bisphosphonate therapy.
After inclusion and subsequently every 6 weeks, fasting venous blood samples
will be drawn. After finishing both interventions (t=12 weeks and t=24 weeks)
patients will be admitted to the clinical research unit for two seperate days,
for an oral glucose tolerance test (OGTT, 75 g oral glucose load) and a
hyperinsulinemic euglycemic clamp. The hyperinsulinemic euglycemic clamp will
be performed using stable isotopes. For the administration of the stable
isotope, glucose and insulin and for blood sampling, intravenous canules will
be inserted in an antecubital vein of each arm. Stable isotopes are not harmful
and hypoglycaemia will not occur because glucose is monitored every 5 minutes.
Total atmitting time on one day will not exceed 7 hours. The total volume of
blood samples from the entire protocol over 6 months will not exceed 500 ml
(blood samples 168 ml, OGTT 12 ml, hyperinsulinemic euglycemic clamp 320 ml).
At t=12 weeks and t=24 weeks patients will also have a whole body dual-energy
X-ray absorptiometry (DXA scan) to measure whole-body fat. DXA radiation
exposure poses a negligible risk.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Male sex
50-80 years
Recently diagnosed primary osteoporosis (T-score between -2.5 and -3.5, no treatment initiated yet) or a recent (clinical) vertebral fracture or two prevalent vertebral fractures independent of bone mineral density (BMD) and subjects with clinical risk factors (recent fracture and T-score * -2.0 or recent repeated falling) and a T-score < -2.5.
Testosterone within reference range
Exclusion criteria
Contraindication to parathyroid hormone therapy: hypersensitivity to the active substrate or to any of the excipients, pre-existing hypercalcaemia, hepatic- or renal insufficiency, metabolic bone diseases other than primary osteoporosis or glucocorticoid-induced osteoporosis, unexplained elevations of alkaline phosphatase, prior external beam or implant radiation therapy to the skeleton, patients with skeletal malignancies or bone metastases ;Any medication or disease influencing bone turnover
Diabetes mellitus
Hypogonadism
Inability to give informed consent
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
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2012-005109-27-NL |
CCMO | NL42624.018.12 |