To assess the impact of 7 daily subcutaneous gifts of GH on circulating Klotho levels in human sugjects with CKD stage III and healthy age-matched controls.
ID
Source
Brief title
Condition
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. To demonstrate the absolute change from baseline to day 7 in sKlotho levels
in serum and urine before and after seven daily subcutaneous gifts of rhGH in
patients with CKD stadium III and age-matched healthy controls.
2. To compare the difference in response between subjects with CKD stage III
and age-matched healthy controls after 7 days of subcutaneous injection of rhGH
on sKlotho levels in serum and urine.
Secondary outcome
Not applicable.
Background summary
The GH * IGF-1 axis is a major controller of cell and tissue growth and
development in human. Stimulation of the pituitary gland under the influence of
hypothalamic hormones leads to pulsatile output of GH from the pituitary,
leading to increased activation of hepatic GH receptors and IGF-1 production.
IGF-1 is a key peptide involved in growth and cellular proliferation. GH and
IGF-1 also have major effects on kidney growth, structure and function and
their overall activities are reduced in patients with CKD.
Klotho is an anti-aging gene and overexpression leads to an extended life span.
Klotho deficiency however, as is the case with patients with CKD, is associated
with premature aging, progression of renal function loss, development of
arterial stiffness, vascular calcification, cardiac hypertrophy, and secondary
hyperparathyroidism. Restoring Klotho levels in different CKD mouse-models
resulted in an impressive amelioration of the kidney injury. Therefore,
upregulation of endogenous Klotho might provide novel treatment strategies not
only to preserve remnant kidney function but also to minimize complications of
CKD. Recent data show that patients with acromegaly, in which the production of
GH and IGF-1 by the anterior pituitary gland is excessive, also have
dramatically elevated levels of sKlotho. After transsphenoidal resection of the
GH-producing adenoma, these elevated sKlotho levels returned rapidly towards
normal. This strongly suggests that GH or IGF-1 are physiological inducers of
Klotho.
Several data suggest that IGF-1 has an important interaction with Klotho
expression and circulating Klotho levels. We hypothesize that exogenously
delivered GH may induce higher levels of Klotho.
In this study, we want to determine the effect of administration of rhGH on
serum levels of Klotho in patients with CKD stage III and compare them with
age-matched controls.
Study objective
To assess the impact of 7 daily subcutaneous gifts of GH on circulating Klotho
levels in human sugjects with CKD stage III and healthy age-matched controls.
Study design
Open, prospective, single-center, nonrandomized, single-arm, explorative trial.
Intervention
All subjects will be administered subcutaneous injections of Somatropin (=
rhGH) of 20 µg/kg/day for 7 subsequent days.
Study burden and risks
The burden and risks associated with participation in this study are:
* 3 extra visits to the VU Medical Center in order to take blood samples and
bring first morning spot urine.
* The subject must receive seven times a subcutaneous dose of Somatropin which
can give local problems at the injection spot like itching and pain.
* The subject can experience side effects of Somatropin, for example peripheral
oedema, headache, joint and muscle complaints.
There are no benefits in participating in this study.
Boelelaan 1117
Amsterdam 1081HV
NL
Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
- Patients with CKD stage III, control group: patients without CKD.
- Patients * 18 years and < 65 years old.
- Providing informed consent.
Exclusion criteria
- Patients who, in the opinion of the study investigator may present a safety risk.
- Patients who are unlikely to adequately comply with the trial*s procedures (due for instance to medical conditions likely to require an extended interruption or discontinuation, history of substance abuse or non-compliance).
- Patients taking medications or having concomitant illnesses likely to confound endpoint assessments (e.g. growth hormone suppletion, thyroid hormone suppletion, use of estrogens, corticosteroids, androgens or anabole steroids, insulin).
- Patients taking other experimental (i.e., non marketed) therapies within a month before preceding screening.
- Patients with any pituitary disease.
- Women who are pregnant, breastfeeding, intend to become pregnant, or not using or willing to use adequate contraception.
- Unwillingness to comply with reproductive precautions. Women who are capable of becoming pregnant must be willing to comply with approved birth control from two-weeks prior to, and for 60 days after taking the investigational product.
- Known growth hormone deficiency.
- History of any malignancy, or active current malignancy.
- Active intracranial tumours.
- BMI > 30.
- History of respiratory disorders or obstructive sleep apnea syndrome (OSAS).
- Critical illness as defined by the need for respiratory or circulatory support (e.g., in an intensive care unit).
- Patients with thyroidal disease.
- Treatment with immunosuppressive agents.
- Patients with active vasculitis.
- Patients with heart failure or a history of heart failure.
- Severe hepatic disease (defined as serum alanine aminotransferase or aspartate aminotransferase levels greater than three times the upper limit of normal).
- Severe chronic systemic infections or inflammatory disease.
- Uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 110 mmHg two times measured).
- Active respiratory infection.
- Patients with diabetes.
- Patients with signs of malnutrition.
- Patients with autosomal dominant polycystic kidney disease (ADPKD).
- Patients with a single kidney.
- Known or suspected allergy to trial product(s) or related products
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 | EUCTR2013-003354-24-NL |
| CCMO | NL45916.029.14 |