In this study we intend to give the label "deuterium" to individuals as heavy water, to determine the turnover parameters of diverse leukocyte populations in health (young adults, healthy seniors of 60 years and older, healthy individuals…
ID
Source
Brief title
Condition
- Other condition
- Immunodeficiency syndromes
Synonym
Health condition
lymfopenie ten gevolge van stamceltransplantatie
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 (delabelling phase). Data obtained during
uplabelling and delabelling phases can be interpreted by mathematical models
that describe the dynamics of leukocyte populations.
Secondary outcome
With the obtained materials several in vitro immunological tests will be
performed, including determination of blood- and plasma levels and analysis of
cell phenotypes and cell numbers within subpopulations.
Background summary
During the last decades, our knowledge of the immune system has been strongly
improved. Still, large controversies exist as to how long the most important
cells of the immune live, how fast they proliferate, and how fast they are
produced in the thymus and bone marrow, under normal, healthy conditions. Lack
of insight in a healthy situation hampers our understanding of how leukocyte
dynamics are changed when the immune system is disturbed, as is the case in
HIV-1 infection or following hematopoietic stem cell transplantation. Thanks to
the combination of the recently developed stable isotope labelling technique
and mathematical modelling it is now possible to study leukocyte dynamics in
vivo, under physiological circumstances.
Study objective
In this study we intend to give the label "deuterium" to individuals as heavy
water, to determine the turnover parameters of diverse leukocyte populations in
health (young adults, healthy seniors of 60 years and older, healthy
individuals that had their thymus removed at young age), and compare these to
situations that disturb the immune system (HIV-1 infection, hematopoietic stem
cell transplantation (HSCT)). Knowledge in these basic parameters is essential
if we want to get more insight in (i) how HIV-1 infection influences leukocyte
dynamics, (ii) how the immune system reconstitutes in HSCT-patients, (iii) what
the contribution of thymus output is in the maintenance of the T cell pool, and
(iv) how ageing influences leukocyte dynamics. Hopefully, a better
understanding of the dynamic basis of such disturbances will also lead to
better perspectives in the development or improvement of therapeutic
interventions.
Study design
The study entails an open observational study, consisting of temporary
consumption of stable-isotope-labelled (deuterated, or heavy) water (2H2O), and
prospective blood and urine sampling for laboratory tests. Blood withdrawals
are done maximally 7 times during the period that heavy water is taken
(uplabelling phase), and maximally 7 or 8 times in the period thereafter
(delabelling phase). From the blood samples several cell populations will be
sorted, after which the deuterium enrichment in DNA isolated from these
populations can be determined by a combination of gas chromatography and mass
spectometry (GC-MS). Frequent sampling of urine permits the correction of label
intake by an individual at a given time point.
Study burden and risks
The physical burden for participants of this study is minimal. Intake of small
amounts of 2H2O as described in this study is not harmful and the daily intake
during the uplabelling phase can take place at home. Only the initial bolus of
2H2O of 10 ml per kg of body weight, which is given in little doses at the day
care, can possibly cause some dizziness or nausea. Blood withdrawals take place
maximally 7 times in the period during which 2H2O is taken (uplabelling phase)
and 7 times in the period after stopping 2H2O intake (delabelling phase). If
necessary and possible, an 15th blood withdrawal will be done at least a year
after stopping 2H2O intake. Hence, participants will visit the UMC Utrecht 14
to 15 times. To restrict personal burden, these visits will, where feasible,
coincide with regular control visits (HSCT patients, HIV-patients), and within
the group of healthy individuals over 60 years the blood withdrawals (except
the first one) will be carried out at the old people's home instead of the UMC
Utrecht . Blood withdrawals can on rare occasions lead to subcutaneous
hematomas.
Lundlaan 6
3584 EA Utrecht
Nederland
Lundlaan 6
3584 EA Utrecht
Nederland
Listed location countries
Age
Inclusion criteria
a. healthy, 20-30 years of age, HIV-negative confirmed with an HIV-test
b. healthy, 60 years or older, HIV-negative confirmed with an HIV-test
c. healthy, 18 years or older, complete thymus removed at young age because of heart surgery, HIV-negative confirmed with an HIV-test
d. stem cell transplantation patiënt, 18 years or older, treated for lymphoma with an autologous HSCT, HIV-negative confirmed with an HIV-test
e. 18 years or older, HIV-1-infected, untreated before and during the study
Exclusion criteria
Participants will be asked to answer a questionnaire which informs us about their health status. Exclusion criteria for each group separately:
a. (i) heart- and/or kidney problems, (ii) immunologic disorder (iii) diabetes, (iv) blood transfusion within the last 6 months, (v) hormone therapy within the last 6 months, (vi) transplantation, (vii) vaccination within the last 4 weeks, (viii) infection and/or fever within the last 4 weeks, (ix) surgery within the last 4 weeks, (x) severe allergy, (xi) for women: pregnancy or parent's wish in the coming year (xii) excessive alcoholic consumption or excessive drug use
b. (i) heart- and/or kidney problems, (ii) immunologic disorder (iii) diabetes, (iv) blood transfusion within the last 6 months, (v) hormone therapy within the last 6 months, (vi) transplantation, (vii) vaccination within the last 4 weeks, (viii) infection and/or fever within the last 4 weeks, (ix) surgery within the last 4 weeks, (x) severe allergy, (xi) excessive alcoholic consumption or excessive drug use
c. (i) heart- and/or kidney problems, (ii) diabetes, (iii) blood transfusion within the last 6 months, (iv) hormone therapy within the last 6 months, (v) transplantation, (vi) vaccination within the last 4 weeks, (vii) infection and/or fever within the last 4 weeks, (viii) surgery within the last 4 weeks, (ix) severe allergy, (x) for women: pregnancy or parent's wish in the coming year (xii) excessive alcoholic consumption or excessive drug use
d. (i) transplantation-related complications, (ii) severe infections (iii) heart- and/or kidney problems, (iv) diabetes, (v) hormone therapy within the last 6 months, (vi) vaccination within the last 4 weeks, (vii) severe allergy, (viii) for women: pregnancy or parent's wish in the coming year (ix) excessive alcoholic consumption or excessive drug use
e. (i) treatment with antiretroviral therapy or expectancy of treatment in the coming year (ii) heart- and/or kidney problems, (iii) diabetes, (iv) blood transfusion within the last 6 months, (v) hormone therapy within the last 6 months, (vi) transplantation, (vii) vaccination within the last 4 weeks, (viii) surgery within the last 4 weeks, (ix) severe allergy, (x) for women: pregnancy or parent's wish in the coming year (xi) excessive alcoholic consumption or excessive drug use
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 |
|---|---|
| CCMO | NL28972.041.09 |