In this study we want to apply heavy water labelling to investigate how ageing affects the dynamics of different leukocyte populations.The main objectives of this study are:(A) to get more insight in the dynamics of an ageing immune system, in order…
ID
Source
Brief title
Condition
- Other condition
- Immunodeficiency syndromes
Synonym
Health condition
immunologische veroudering
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main parameter of the study is the amount of deuterium (label) that the
different leukocyte populations have incorporated in their DNA by cell division
at a given time. For this purpose blood withdrawals are done both in the period
during which participants drink 2H2O (uplabelling phase) and in the period
after stopping with 2H2O intake (downlabelling phase). Data obtained during
uplabelling and downlabelling phases can be interpreted by mathematical models
that describe the dynamics of leukocyte populations.
Secondary outcome
With the obtained materials several in vitro immunological test will be
performed, including determination of blood- and plasma levels and analysis of
cell phenotypes and cell numbers within subpopulations.
Background summary
Ageing of the immune system plays an important role in the development of
various age-related health problems among elderly, e.g. increased
susceptibility to infections and reduced vaccine efficiency. During ageing
dramatic changes take place in the immune system: the number of total and naive
lymphocytes declines and important shifts between subpopulations take place. To
explain what is causing these changes we want to quantify how the dynamics of
leukocytes (expressed in terms of production rate and lifespan) change as
people age. Quantitative insights in these dynamics will facilitate the
tackling of the problems of immune and vaccine failure in elderly. Moreover the
availability of reference values of healthy dynamics will allow for a fair
comparison of patients with healthy controls of matching age.
Study objective
In this study we want to apply heavy water labelling to investigate how ageing
affects the dynamics of different leukocyte populations.
The main objectives of this study are:
(A) to get more insight in the dynamics of an ageing immune system, in order to
improve our understanding of what is causing immune-related health problems in
the elderly.
(B) to obtain reference values for leukocyte dynamics in healthy young and
healthy older individuals, in order to
(i) get more insight in how these dynamics change in various patient
populations (compared to healthy individuals of matched age);
(ii) investigate how certain pathological situations can lead to premature
ageing of the immune system.
Study design
The study concerns longitudinal observational research with invasive acts. It
is composed of temporary consumption of deuterated (heavy) water (2H2O) and
prospective blood withdrawals and urine sampling for laboratory research. Blood
is drawn 7 times in the period during which participants drink heavy water
(uplabelling phase) and 8 times in the period that follows (downlabelling
phase). From the blood samples various leukocyte populations will be sorted
after which in the DNA of these samples deuterium enrichment can be quantified
using gas chromatography and mass spectrometry (GC-MS). Frequent sampling of
urine makes it possible to correct, per time point, for the intake of deuterium
by an individual.
Study burden and risks
The frequent blood- and urine sampling and associated hospital visits make the
burden of this study substantial. In addition, the questionnaires can be
considered an incursion on one's privacy. There is no direct advantage of
participation. The necessary amounts of heavy water are not harmful. The total
volume of withdrawn blood falls within the limits applied by Sanquin Bloedbank.
Safety of heavy water for human consumption is reaffirmed with a test.
Participation hence comes with burden, but is safe.
Lundlaan 6
3584 EA Utrecht
NL
Lundlaan 6
3584 EA Utrecht
NL
Listed location countries
Age
Inclusion criteria
5 healthy young individuals; 20-25 years of age
10 healthy older individuals; at least 60 years of age
Exclusion criteria
(i) Infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV);
(ii) Other severe infections, e.g. malaria, infectious mononucleosis, a sexually transmitted disease (STD);
(iii) Hayfever or allergy;
(iv) Asthma or COPD;
(v) Diabetes;
(vi) Auto-immune disease, e.g. rheumatoid arthritis;
(vii) Heart problems, or a history of heart problems;
(viii) Kidney problemns, or a history of kidney problems;
(ix) Chest pain or shortage of breath, in rest or during exercise;
(x) Body weight of less than 50 kg;
(xi) Use of medication, with the exception of (a) analgesics when taken less frequent than weekly (paracetamol, ibuprofen, aspirin) (b) contraceptives;
(xii) History of cancer;
(xiii) Pregnancy or parent's wish in the coming year;
(xiv) Excessive alcohol consumption;
(xv) Drug use;
(xvi) Changing and unsafe sexual contacts;
(xvii) Sexual contact with an individual infected with HIV or another STD within the last 12 months;
(xviii) Extreme sensitivity to car-sickness and/or sea-sickness
Design
Recruitment
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
CCMO | NL30762.041.10 |