Leukocyte Adhesion Deficiency SyndromePhase 2NCT00001905
Interferon Gamma to Treat Leukocyte Adhesion Deficiency Type I
A Phase 2 study testing Interferon gamma in people with Leukocyte Adhesion Deficiency Syndrome, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will evaluate the safety and effectiveness of the drug, interferon gamma, in treating leukocyte adhesion deficiency type I (LAD I). Patients with this inherited immune disorder do not have enough proteins called adhesion molecules on their infection-fighting white blood cells, impairing the ability of these… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Leukocyte Adhesion Deficiency Syndrome
- What is being tested?
- Interferon gamma
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 1999to Mar 2002
- Phase
- Phase 2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
PARTICIPANT INCLUSION CRITERIA:
Leukocyte Adhesion Deficiency type I, as determined by flow cytometry showing less than 10% CD18 expression in association with typical signs of LAD I .
Weight adequate to permit the blood drawing requirements of the protocol, greater than 13 kg.
Patients should be without serious, ongoing, uncontrolled infections.
Adequate hematopoietic, renal and hepatic function, defined as:
Absolute neutrophil count greater than or equal to 1500/microL;
Hemoglobin greater than or equal to 7g/dL (post transfusion or erythropoeitin);
Platelet count greater than or equal to 100,000/microL;
Creatinine less than or equal to 1.5 x upper limit of normal;
Bilirubin less than or equal to 1.5 x upper limit of normal;
AST/SGOT less than or equal to 2.5 x upper limit of normal;
ALT/SGPT less than or equal to 2.5 x upper limit of normal;
Calculated Creatinine Clearance greater than or equal to 60 mL/min.
Karnofsky Performance Status Index greater than or equal to 70.
Written signed informed consent.
PARTICIPANT EXCLUSION CRITERIA:
HIV infection.
Active malignancy.
Symptomatic cardiac disease or ongoing treatment for same.
Pregnant or lactating women.
Surgery during the two weeks prior to the start of IFN-gamma dosing.
Concurrent use of systemic corticosteroids, except for physiologic replacement.
Exposure to any investigational drug within four weeks prior to the start of dosing.
Any other major illness which, in the investigator's judgement, may substantially increase the risk associated with the patients participation in this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, 20892
About this study
Official title: Interferon Gamma Administration in Leukocyte Adhesion Deficiency Type I
This study will evaluate the safety and effectiveness of the drug, interferon gamma, in treating leukocyte adhesion deficiency type I (LAD I). Patients with this inherited immune disorder do not have enough proteins called adhesion molecules on their infection-fighting white blood cells, impairing the ability of these cells to get to the site of infection. As a result, patients have recurrent infections of soft tissues, such as the skin, gums and gastrointestinal tract, and poor wound healing. Infants with severe LAD I often die from multiple infections. Interferon gamma may increase the number of adhesion molecules on white blood cells, and thus improve their function.
Patients with LAD I who weigh more than 13 kilograms (28.5 pounds) may be eligible for this study. Candidates will have personal and family medical histories taken, a physical examination, blood and urine tests and a chest X-ray or computed tomography (CT) scan.
Read more
Participants will receive injections of interferon gamma under the skin 3 times a week for 3 months. Adult patients will be taught how to give their own injections (similar to insulin injections for diabetes) and parents will be taught how to administer the shots to their child. Blood samples, usually be between 30 to 90 milliliters (2 to 6 tablespoons), will be drawn just before starting medication and again 1 day, 1 week, 1 month, 3 months and 4 months after therapy begins. At these same time intervals, patients will provide a salt-water mouth rinse specimen, which will be tested for changes in the number of white blood cells during interferon gamma treatment.
Patients will be admitted to the NIH Clinical Center for inpatient evaluations at the start of therapy and again after 1 week, 1month, 3 months and 4 months. The initial screening visit will take a few days and subsequent visits will take 1 to 2 days.
Read the detailed description
Leukocyte adhesion deficiency type I (LAD I) is a primary immunodeficiency disease resulting from mutations in the gene encoding CD18. Markedly reduced or absent expression of the leukocyte integrin component CD18 causes significant impairment in leukocyte mobilization to inflammatory sites. Clinically, patients have marked leukocytosis and recurrent infections involving soft tissues such as skin, the gastrointestinal tract and gingiva. Death due to infections in early infancy is common with the severe form of LAD I (CD18 expression less than 0.5%), but patients with the moderate phenotype (CD18 expression 1-10%) may survive into young adulthood. To date, therapy consists of antibiotic treatment for infections and bone marrow transplantation when possible. LAD I is also a candidate for future gene therapy. Recently, it has been shown that in vivo administration of interferon gamma (IFN-gamma) upregulates CD18 expression in normals and alters leukocyte trafficking. We hypothesize that modest increases in CD18 expression in LAD I patients with the moderate phenotype or alterations in CD18 independent trafficking could result in detectable clinical changes and possible clinical improvement.
- Conditions
- Leukocyte Adhesion Deficiency Syndrome
- Being tested
- Interferon gamma
- Keywords
- Neutrophil, Immunodeficiency, Cytokine, Treatment, Trafficking, Leukocyte Adhesion Deficiency Type I, LAD I
- Medical subject headings
- Leukocyte-Adhesion Deficiency Syndrome, Immunologic Deficiency Syndromes, Leukocyte adhesion deficiency type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interferon gammaDrug
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 startApr 1999
- Study completionMar 2002
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 Leukocyte Adhesion Deficiency SyndromeStudies 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 2
- Primary purpose
- Treatment
- Enrolment
- 5 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001905
- Sponsor's protocol ID
- 990089
- Other IDs
- 99-I-0089
- Status last verified
- Mar 2002
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Anderson DC, Springer TA. Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med. 1987;38:175-94. doi: 10.1146/annurev.me.38.020187.001135.
PubMed 3555290Schiff DE, Rae J, Martin TR, Davis BH, Curnutte JT. Increased phagocyte Fc gammaRI expression and improved Fc gamma-receptor-mediated phagocytosis after in vivo recombinant human interferon-gamma treatment of normal human subjects. Blood. 1997 Oct 15;90(8):3187-94.
PubMed 9376602Anderson DC, Schmalsteig FC, Finegold MJ, Hughes BJ, Rothlein R, Miller LJ, Kohl S, Tosi MF, Jacobs RL, Waldrop TC, et al. The severe and moderate phenotypes of heritable Mac-1, LFA-1 deficiency: their quantitative definition and relation to leukocyte dysfunction and clinical features. J Infect Dis. 1985 Oct;152(4):668-89. doi: 10.1093/infdis/152.4.668.
PubMed 3900232
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interferon Gamma Administration in Leukocyte Adhesion Deficiency Type I
- ClinicalTrials.gov ID
- NCT00001905
- Acronym / sponsor ID
- 990089
- Conditions
- Leukocyte Adhesion Deficiency Syndrome
- Keywords
- Neutrophil, Immunodeficiency, Cytokine, Treatment, Trafficking, Leukocyte Adhesion Deficiency Type I, LAD I
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Apr 1999
- Study completion
- Mar 2002
- 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 evaluate the safety and effectiveness of the drug, interferon gamma, in treating leukocyte adhesion deficiency type I (LAD I). Patients with this inherited immune disorder do not have enough proteins called adhesion molecules on their infection-fighting white blood cells, impairing the ability of these cells to get to the site of infection. As a result, patients have recurrent infections of soft tissues, such as the skin, gums and gastrointestinal tract, and poor wound healing. Infants with severe LAD I often die from multiple infections. Interferon gamma may increase the number of adhesion molecules on white blood cells, and thus improve their function.
Patients with LAD I who weigh more than 13 kilograms (28.5 pounds) may be eligible for this study. Candidates will have personal and family medical histories taken, a physical examination, blood and urine tests and a chest X-ray or computed tomography (CT) scan.
Participants will receive injections of interferon gamma under the skin 3 times a week for 3 months. Adult patients will be taught how to give their own injections (similar to insulin injections for diabetes) and parents will be taught how to administer the shots to their child. Blood samples, usually be between 30 to 90 milliliters (2 to 6 tablespoons), will be drawn just before starting medication and again 1 day, 1 week, 1 month, 3 months and 4 months after therapy begins. At these same time intervals, patients will provide a salt-water mouth rinse specimen, which will be tested for changes in the number of white blood cells during interferon gamma treatment.
Patients will be admitted to the NIH Clinical Center for inpatient evaluations at the start of therapy and again after 1 week, 1month, 3 months and 4 months. The initial screening visit will take a few days and subsequent visits will take 1 to 2 days.
Detailed description
Leukocyte adhesion deficiency type I (LAD I) is a primary immunodeficiency disease resulting from mutations in the gene encoding CD18. Markedly reduced or absent expression of the leukocyte integrin component CD18 causes significant impairment in leukocyte mobilization to inflammatory sites. Clinically, patients have marked leukocytosis and recurrent infections involving soft tissues such as skin, the gastrointestinal tract and gingiva. Death due to infections in early infancy is common with the severe form of LAD I (CD18 expression less than 0.5%), but patients with the moderate phenotype (CD18 expression 1-10%) may survive into young adulthood. To date, therapy consists of antibiotic treatment for infections and bone marrow transplantation when possible. LAD I is also a candidate for future gene therapy. Recently, it has been shown that in vivo administration of interferon gamma (IFN-gamma) upregulates CD18 expression in normals and alters leukocyte trafficking. We hypothesize that modest increases in CD18 expression in LAD I patients with the moderate phenotype or alterations in CD18 independent trafficking could result in detectable clinical changes and possible clinical improvement.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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 |
|---|---|---|
| Interferon gamma | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 3555290Anderson DC, Springer TA. Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med. 1987;38:175-94. doi: 10.1146/annurev.me.38.020187.001135.
- Background: PubMed 9376602Schiff DE, Rae J, Martin TR, Davis BH, Curnutte JT. Increased phagocyte Fc gammaRI expression and improved Fc gamma-receptor-mediated phagocytosis after in vivo recombinant human interferon-gamma treatment of normal human subjects. Blood. 1997 Oct 15;90(8):3187-94.
- Background: PubMed 3900232Anderson DC, Schmalsteig FC, Finegold MJ, Hughes BJ, Rothlein R, Miller LJ, Kohl S, Tosi MF, Jacobs RL, Waldrop TC, et al. The severe and moderate phenotypes of heritable Mac-1, LFA-1 deficiency: their quantitative definition and relation to leukocyte dysfunction and clinical features. J Infect Dis. 1985 Oct;152(4):668-89. doi: 10.1093/infdis/152.4.668.
Related trials for Leukocyte Adhesion Deficiency Syndrome
RecruitingObservational study
Evaluation of Patients With Immune Function Abnormalities
Chronic Granulomatous Disease (CGD), X-Linked Severe Combined Immune Deficiency (XSCID)
RecruitingObservational study
Data Collection Study of Patients With Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT With RIC
Primary Immunodeficiency (PID), Congenital Bone Marrow Failure Syndromes
RecruitingPhase 2
Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT
Primary Immunodeficiency (PID), Congenital Bone Marrow Failure Syndromes
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Interferon gamma in people with Leukocyte Adhesion Deficiency Syndrome, 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.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001905, 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 4 Mar 2008; AzTrials last refreshed its copy on 7 Nov 2026.