HIVNCT00001651
Use of Labeled Glucose to Study Lymphocyte Replication and Survival in HIV-Infected Patients
A study testing [6,6-2H2]-glucose in people with HIV and Healthy Volunteers, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will examine how quickly white blood cells called CD4 lymphocytes replicate (divide) and how long they live in both HIV-infected and non-infected people by measuring how quickly the genetic material (DNA) of cells is replicated. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- HIV, Healthy Volunteers
- What is being tested?
- [6,6-2H2]-glucose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Feb 1998to 29 May 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- FOR PATIENTS:
- 18 years or older.
- Able to provide informed consent and willing to comply with study requirements and clinic policies.
- Negative urine pregnancy test (for women of childbearing potential).
- Hemoglobin greater than 10 mg/dl.
- Adequate venous access in the arms for blood drawing and 5 day infusions, and lymphapheresis
Show all 11Show fewer
- Willingness to allow stored samples to be used for future studies of HIV infection and/or immunological function, and willingness to have HLA typing performed. (For previously enrolled patients, patients would be requested, but not required, to provide permission to use stored samples in the future, and to permit HLA testing
- FOR HIV POSITIVE PATIENTS:
- Documented HIV infection (ELISA/Western blot positive or, for acute seroconverters, PCR positive).
- FOR HIV NEGATIVE PATIENTS:
- Negative ELISA/Western blot.
Who cannot join
- Diabetes mellitus requiring drug therapy.
- Active substance abuse or prior history of substance abuse which may interfere with protocol compliance.
- Psychiatric illness or disturbance which, in the assessment of the protocol team, may affect patient safety or compliance.
- Significant underlying cardiac, pulmonary, renal, gastrointestinal, rheumatologic or CNS disease as detectable on routine history, physical exam, or screening laboratory studies. Patients would be excluded if they had an acute or chronic underlying medical problem that in the judgment of the principal investigator could be exacerbated by participating in the protocol or that would make it difficult for them to comply with the protocol requirements.
- Pregnancy or breast-feeding.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Studies of Lymphocyte Kinetics Using Stable Isotopes
This study will examine how quickly white blood cells called CD4 lymphocytes replicate (divide) and how long they live in both HIV-infected and non-infected people by measuring how quickly the genetic material (DNA) of cells is replicated. To do this, participants will receive infusions of glucose, a non-radioactive form of a type of sugar. Cells normally use glucose to make various products needed for cell growth and replication, including cell DNA. Measuring how much glucose cells incorporate into their DNA can provide important information about cell replication. This rate of incorporation will be examined and compared in HIV-infected people and in healthy, normal volunteers.
HIV-infected patients and non-infected healthy volunteers 18 years of age and older may be eligible for this study. Candidates will be screened with a medical history, physical examination, chest X-ray, electrocardiogram (EKG) and blood tests.
Read more
Participants will be given a continuous infusion of glucose at a dose of up to 60 grams (about 2 ounces) per day for up to 5 days. The glucose will be delivered through a catheter (thin plastic tube) placed in an arm vein. Blood samples will be collected as often as daily in the first week following the infusion and then from twice a week to once a month for up to 4 years. Alternatively, patients may undergo leukapheresis a procedure for collecting quantities of lymphocytes up to 10 times during the first month after the infusion, and possibly later as well, but no more often than once every 2 weeks. For this procedure, whole blood is collected through a needle in an arm vein. The blood circulates through a machine that separates it into its components. The white cells are removed and the rest of the blood is returned to the body either through the same needle or through a second needle in the other arm. Participants may be asked to receive up to four glucose infusions. There will be at least a 2-week interval between infusions. Participants who have more than three leukapheresis procedures within 3 weeks will have at least 6 weeks between infusions.
Participants will be followed periodically in the outpatient clinic for evaluation and tests.
This study may provide a better understanding of how HIV causes disease and progressive weakening of the immune system and how therapies affect immunity.
Read the detailed description
Understanding the rate of lymphocyte replication and destruction in HIV-infected patients, as well as the effects of therapy on lymphocyte replication should lead to a better understanding of the mechanisms behind the immunodeficiency induced by HIV. To examine this directly, up to 100 HIV-infected patients will receive up to 5 days of continuous infusions with [6,6-(2)H(2)]-glucose, a nonradioactive, stable isotope of glucose that is safe to administer. The deuterium is incorporated into DNA via metabolism of glucose to ribose and incorporation into nucleotides. The rate of incorporation can be measured in subpopulations of cells to determine the rate of replication of those cells. Fifty HIV-uninfected persons will also be enrolled in the protocol to allow a determination of lymphocyte kinetics in individuals with normally functioning immune systems or immune systems that may have been affected by other diseases. All participants in this study will be reimbursed for the inconvenience and discomfort associated with study participation.
- Conditions
- HIV, Healthy Volunteers
- Being tested
- [6,6-2H2]-glucose
- Keywords
- HIV Infection, Lymphocyte Turnover
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[6,6-2H2]-glucoseOther
[6,6-2H2]-glucose will be administered as a continuous IV infusion for one to five days.
| Study group | Role | What they receive |
|---|---|---|
| HIV-infected subjects | Experimental | HIV-infected adults Receives: Other: [6,6-2H2]-glucose |
| HIV-negative subjects | Experimental | HIV-negative adults Receives: Other: [6,6-2H2]-glucose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Kinetics of lymphocyte turnover
Cell turnover markers
Measured: Day 2, 5 (end of [6,6-2H2]-glucose infusion), 6, 8, 12, 16, 20, and 28. After day 28, visits will occur monthly through 6 months, then no more often than every 3 months through 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start25 Feb 1998
- Primary completion1 Jan 2020
- Study completion29 May 2020
Why it stopped: Slow/Insufficient accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- \[6,6-2H2\]-glucose will be administered as a continuous IV infusion for one to five days. Blood (approximately 30-50 ml) will be drawn every one to three days during the infusion to obtain cells for analysis. In addition, serum glucose will be checked every two to three days. Following completion of the infusion, blood may be drawn daily for the first week, and then twice weekly for an additional 3 weeks, and then weekly to monthly.
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Joseph A Kovacs, M.D., Principal investigator, National Institutes of Health Clinical Center (CC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001651
- Sponsor's protocol ID
- 970191
- Other IDs
- 97-I-0191
- Status last verified
- May 2020
- First submitted
- 3 Nov 1999
- Last updated
- 1 Jun 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Wolthers KC, Bea G, Wisman A, Otto SA, de Roda Husman AM, Schaft N, de Wolf F, Goudsmit J, Coutinho RA, van der Zee AG, Meyaard L, Miedema F. T cell telomere length in HIV-1 infection: no evidence for increased CD4+ T cell turnover. Science. 1996 Nov 29;274(5292):1543-7. doi: 10.1126/science.274.5292.1543.
PubMed 8929418Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995 Jan 12;373(6510):123-6. doi: 10.1038/373123a0.
PubMed 7816094Hellerstein MK. Methods for measurement of fatty acid and cholesterol metabolism. Curr Opin Lipidol. 1995 Jun;6(3):172-81. doi: 10.1097/00041433-199506000-00010.
PubMed 7648007
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Studies of Lymphocyte Kinetics Using Stable Isotopes
- ClinicalTrials.gov ID
- NCT00001651
- Acronym / sponsor ID
- 970191
- Conditions
- HIV, Healthy Volunteers
- Keywords
- HIV Infection, Lymphocyte Turnover
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow/Insufficient accrual
- Enrolment
- 54 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 25 Feb 1998 (actual)
- Primary completion
- 1 Jan 2020 (actual)
- Study completion
- 29 May 2020 (actual)
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine how quickly white blood cells called CD4 lymphocytes replicate (divide) and how long they live in both HIV-infected and non-infected people by measuring how quickly the genetic material (DNA) of cells is replicated. To do this, participants will receive infusions of glucose, a non-radioactive form of a type of sugar. Cells normally use glucose to make various products needed for cell growth and replication, including cell DNA. Measuring how much glucose cells incorporate into their DNA can provide important information about cell replication. This rate of incorporation will be examined and compared in HIV-infected people and in healthy, normal volunteers.
HIV-infected patients and non-infected healthy volunteers 18 years of age and older may be eligible for this study. Candidates will be screened with a medical history, physical examination, chest X-ray, electrocardiogram (EKG) and blood tests.
Participants will be given a continuous infusion of glucose at a dose of up to 60 grams (about 2 ounces) per day for up to 5 days. The glucose will be delivered through a catheter (thin plastic tube) placed in an arm vein. Blood samples will be collected as often as daily in the first week following the infusion and then from twice a week to once a month for up to 4 years. Alternatively, patients may undergo leukapheresis a procedure for collecting quantities of lymphocytes up to 10 times during the first month after the infusion, and possibly later as well, but no more often than once every 2 weeks. For this procedure, whole blood is collected through a needle in an arm vein. The blood circulates through a machine that separates it into its components. The white cells are removed and the rest of the blood is returned to the body either through the same needle or through a second needle in the other arm. Participants may be asked to receive up to four glucose infusions. There will be at least a 2-week interval between infusions. Participants who have more than three leukapheresis procedures within 3 weeks will have at least 6 weeks between infusions.
Participants will be followed periodically in the outpatient clinic for evaluation and tests.
This study may provide a better understanding of how HIV causes disease and progressive weakening of the immune system and how therapies affect immunity.
Detailed description
Understanding the rate of lymphocyte replication and destruction in HIV-infected patients, as well as the effects of therapy on lymphocyte replication should lead to a better understanding of the mechanisms behind the immunodeficiency induced by HIV. To examine this directly, up to 100 HIV-infected patients will receive up to 5 days of continuous infusions with [6,6-(2)H(2)]-glucose, a nonradioactive, stable isotope of glucose that is safe to administer. The deuterium is incorporated into DNA via metabolism of glucose to ribose and incorporation into nucleotides. The rate of incorporation can be measured in subpopulations of cells to determine the rate of replication of those cells. Fifty HIV-uninfected persons will also be enrolled in the protocol to allow a determination of lymphocyte kinetics in individuals with normally functioning immune systems or immune systems that may have been affected by other diseases. All participants in this study will be reimbursed for the inconvenience and discomfort associated with study participation.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- [6,6-2H2]-glucose will be administered as a continuous IV infusion for one to five days. Blood (approximately 30-50 ml) will be drawn every one to three days during the infusion to obtain cells for analysis. In addition, serum glucose will be checked every two to three days. Following completion of the infusion, blood may be drawn daily for the first week, and then twice weekly for an additional 3 weeks, and then weekly to monthly.
| Arm | Type | Receives |
|---|---|---|
| HIV-infected subjects | Experimental | Other: [6,6-2H2]-glucoseHIV-infected adults |
| HIV-negative subjects | Experimental | Other: [6,6-2H2]-glucoseHIV-negative adults |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 18 years or older.
- Able to provide informed consent and willing to comply with study requirements and clinic policies.
- Negative urine pregnancy test (for women of childbearing potential).
- Hemoglobin greater than 10 mg/dl.
- Adequate venous access in the arms for blood drawing and 5 day infusions, and lymphapheresis
Key exclusion criteria (5 listed)
- Diabetes mellitus requiring drug therapy.
- Active substance abuse or prior history of substance abuse which may interfere with protocol compliance.
- Psychiatric illness or disturbance which, in the assessment of the protocol team, may affect patient safety or compliance.
- Significant underlying cardiac, pulmonary, renal, gastrointestinal, rheumatologic or CNS disease as detectable on routine history, physical exam, or screening laboratory studies. Patients would be excluded if they had an acute or chronic underlying medical problem that in the judgment of the principal investigator could be exacerbated by participating in the protocol or that would make it difficult for them to comply with the protocol requirements.
- Pregnancy or breast-feeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [6,6-2H2]-glucose[6,6-2H2]-glucose will be administered as a continuous IV infusion for one to five days. | Other | HIV-infected subjects, HIV-negative subjects |
Primary outcome
Kinetics of lymphocyte turnover
Time frame: Day 2, 5 (end of [6,6-2H2]-glucose infusion), 6, 8, 12, 16, 20, and 28. After day 28, visits will occur monthly through 6 months, then no more often than every 3 months through 2 years.
Cell turnover markers
Results and safety
The study was stopped early (reason given: Slow/Insufficient accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2020.
- Background: PubMed 8929418Wolthers KC, Bea G, Wisman A, Otto SA, de Roda Husman AM, Schaft N, de Wolf F, Goudsmit J, Coutinho RA, van der Zee AG, Meyaard L, Miedema F. T cell telomere length in HIV-1 infection: no evidence for increased CD4+ T cell turnover. Science. 1996 Nov 29;274(5292):1543-7. doi: 10.1126/science.274.5292.1543.
- Background: PubMed 7816094Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995 Jan 12;373(6510):123-6. doi: 10.1038/373123a0.
- Background: PubMed 7648007Hellerstein MK. Methods for measurement of fatty acid and cholesterol metabolism. Curr Opin Lipidol. 1995 Jun;6(3):172-81. doi: 10.1097/00041433-199506000-00010.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph A Kovacs, M.D. principal investigator
National Institutes of Health Clinical Center (CC)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing [6,6-2H2]-glucose in people with HIV and Healthy Volunteers, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Slow/Insufficient accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Kinetics of lymphocyte turnover (time frame: Day 2, 5 (end of [6,6-2H2]-glucose infusion), 6, 8, 12, 16, 20, and 28. After day 28, visits will occur monthly through 6 months, then no more often than every 3 months through 2 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001651, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2020.