Treatment of Deficient Subclass or Anti-polysaccharide Antibody Response - Full Text View

Sponsor:	Sanquin
Information provided by:	Sanquin
ClinicalTrials.gov Identifier:	NCT00522821

Purpose

There is no consensus on the treatment of patients with recurrent infections and isolated immunoglobulin G (IgG)-subclass deficiency and/or selective antipolysaccharide antibody deficiency. Therefore, the Dutch Inter University Working Party will start a study in which the treatment with antibiotics is compared with intravenous immunoglobulin therapy with respect to clinical outcome measures in both children and adults with this disorder.

Condition	Intervention	Phase
IgG Deficiency Infections	Drug: intravenous immunoglobulins Drug: co-trimoxazole	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	Treatment in Patients With Recurrent Infections and IgG Subclass Deficiency, and/or Deficient Anti-Polysaccharide Antibody Response

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia complement factor I deficiency X-linked hyper IgM syndrome

Drug Information available for: Immunoglobulins Trimethoprim-sulfamethoxazole combination Globulin, Immune

U.S. FDA Resources

Further study details as provided by Sanquin:

Primary Outcome Measures:

the number, duration and type of infection (including use of antibiotics to treat infections), days of fever, hospital admissions and, if applicable, days absent from school or work due to infections. [ Time Frame: 27 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety will be monitored by occurrence of adverse events, vital signs, and laboratory measurements. [ Time Frame: 27 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	November 2007
Estimated Study Completion Date:	November 2014
Estimated Primary Completion Date:	May 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A A: co-trimoxazole prophylactically for 12 months followed by intravenous immunoglobulin treatment for 12 months. Treatments will be separated by a washout period of 3 months during which co-trimoxazole will be given.	Drug: intravenous immunoglobulins Adults: 600 mg/kg bodyweight every 3 weeks Children: 800 mg/kg bodyweight every 3 week Other Name: Nanogam Drug: co-trimoxazole Children ≥5-12: If well tolerated, 4 mg trimethoprim and 20 mg sulfamethoxazole per kg bodyweight once daily, every day of the week (max160/800mg/day), combined with 5 mg folic acid. Adults and children ≥12 years or ≥40 kg: If well tolerated, 160 mg trimethoprim and 800 mg sulfamethoxazole once daily, every day of the week combined with 5 mg folic acid.
B B: intravenous immunoglobulin treatment for 12 months followed by co-trimoxazole prophylactically for 12 months. Treatments will be separated by a washout period of 3 months during which co-trimoxazole will be given.	Drug: intravenous immunoglobulins Adults: 600 mg/kg bodyweight every 3 weeks Children: 800 mg/kg bodyweight every 3 week Other Name: Nanogam Drug: co-trimoxazole Children ≥5-12: If well tolerated, 4 mg trimethoprim and 20 mg sulfamethoxazole per kg bodyweight once daily, every day of the week (max160/800mg/day), combined with 5 mg folic acid. Adults and children ≥12 years or ≥40 kg: If well tolerated, 160 mg trimethoprim and 800 mg sulfamethoxazole once daily, every day of the week combined with 5 mg folic acid.

Arms

Assigned Interventions

A

A: co-trimoxazole prophylactically for 12 months followed by intravenous immunoglobulin treatment for 12 months.

Treatments will be separated by a washout period of 3 months during which co-trimoxazole will be given.

Drug: intravenous immunoglobulins

Adults: 600 mg/kg bodyweight every 3 weeks
Children: 800 mg/kg bodyweight every 3 week

Other Name: Nanogam

Drug: co-trimoxazole

Children ≥5-12: If well tolerated, 4 mg trimethoprim and 20 mg sulfamethoxazole per kg bodyweight once daily, every day of the week (max160/800mg/day), combined with 5 mg folic acid.
Adults and children ≥12 years or ≥40 kg: If well tolerated, 160 mg trimethoprim and 800 mg sulfamethoxazole once daily, every day of the week combined with 5 mg folic acid.

B

B: intravenous immunoglobulin treatment for 12 months followed by co-trimoxazole prophylactically for 12 months.

Treatments will be separated by a washout period of 3 months during which co-trimoxazole will be given.

Drug: intravenous immunoglobulins

Adults: 600 mg/kg bodyweight every 3 weeks
Children: 800 mg/kg bodyweight every 3 week

Other Name: Nanogam

Drug: co-trimoxazole

Children ≥5-12: If well tolerated, 4 mg trimethoprim and 20 mg sulfamethoxazole per kg bodyweight once daily, every day of the week (max160/800mg/day), combined with 5 mg folic acid.
Adults and children ≥12 years or ≥40 kg: If well tolerated, 160 mg trimethoprim and 800 mg sulfamethoxazole once daily, every day of the week combined with 5 mg folic acid.

Detailed Description:

There is no consensus on the treatment of patients with recurrent infections and isolated IgG-subclass deficiency and/or selective antipolysaccharide antibody deficiency. At present, there are no robust criteria to predict which patient will or will not respond adequately to antibiotic treatment or to IVIG. Furthermore, it is unknown whether IVIG treatment improves the quality of life in these patients. Therefore, the Dutch InterUniversity Working Party intends to start a study in this patient group. In this study, treatment for a year with antibiotics will be compared with a year intravenous immunoglobulin therapy with respect to clinical outcome measures in both children and adults with this disorder.

The patient will visit the clinic every 3 months during which laboratory tests and physiological measurements will be performed. Moreover the occurrence of infections and fever, the use of antibiotics, hospital admissions, and quality of life will be documented.

The study should result in a national harmonization in the treatment of this patient group. To this end, the results of the study will be used to compile a treatment protocol for this group of patients in the Netherlands and if applicable also in other countries worldwide.

Eligibility

Ages Eligible for Study:	5 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

IgG subclass deficiency and/or (selective) antipolysaccharide antibody deficiency
At least 2 physician documented infections before the start of the current treatment or in the last 6 months for newly diagnosed patients.
Total serum IgG > 4 g/l
≥ 5 years of age
Informed consent

Exclusion Criteria:

Treatment with any other investigational drug within 7 days prior to study entry, or previous enrolment in this study
Allergic reactions against human plasma/plasma products, or co-trimoxazole
An ongoing progressive terminal disease
Pregnancy or lactation
History of (transient) cerebrovascular accident or coronary insufficiency
Renal insufficiency (plasma creatinin > 115 µmol/L; or creatinin clearance <20 ml/min)
An ongoing active disease causing general symptoms e.g. chronic active hepatitis or persistent enterovirus infection with ongoing systemic complaints
Detectable anti-IgA antibodies
Active systemic lupus erythematosus (SLE)
Glucose-6-phosphate hydrogenase deficiency

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00522821

Contacts

Contact: P S Strengers, MD		p.strengers@sanquin.nl
Contact: I Kleine Budde, PhD		i.kleinebudde@sanquin.nl

Locations

Netherlands
VU	Not yet recruiting
Amsterdam, Netherlands
Contact: M A van Agtmael, PhD,MD
Principal Investigator: M van Agtmael
AMC	Recruiting
Amsterdam, Netherlands
Contact: R JM ten Berge, PhD, MD
Contact: T W Kuijpers, PhD, MD
Principal Investigator: R JM ten Berge, PhD, MD
Principal Investigator: T W Kuijpers, PhD, MD
Jeroen Bosch Ziekenhuis	Recruiting
Den Bosch, Netherlands
Contact: E de Vries, PhD,MD
Principal Investigator: E de Vries, PhD,MD
UMCG	Recruiting
Groningen, Netherlands
Contact: C GM Kallenberg, PhD,MD
Principal Investigator: C GM Kallenberg, PhD,MD
LUMC	Recruiting
Leiden, Netherlands
Contact: J T van Dissel, PhD, MD
Contact: M J Van Tol, PhD, MD
Principal Investigator: J T van Dissel, PhD,MD
Principal Investigator: M J van Tol, PhD,MD
Principal Investigator: R G Bredius, PhD,MD
AZM	Recruiting
Maastricht, Netherlands
Contact: J W Cohen Tervaert, PhD, MD
Principal Investigator: J W Cohen Tervaert, PhD, MD
UMC St Radboud	Recruiting
Nijmegen, Netherlands
Contact: M van Deuren, PhD,MD
Contact: A Warris, PhD,MD
Principal Investigator: M van Deuren, PhD,MD
Principal Investigator: A Warris, PhD,MD
Erasmus MC	Recruiting
Rotterdam, Netherlands
Contact: P M van Hagen, PhD, MD
Contact: N G Hartwig, PhD, MD
Principal Investigator: P M van Hagen, PhD, MD
Principal Investigator: N G Hartwig, PhD, MD
UMCU	Recruiting
Utrecht, Netherlands
Contact: E AM Sanders, PhD,MD
Contact: I M Hoepelman, PhD,MD
Principal Investigator: E AM Sanders, PhD,MD
Principal Investigator: I M Hoepelman, PhD,MD
Principal Investigator: G Rijkers, PhD

Sponsors and Collaborators

Sanquin

Investigators

Principal Investigator:	J T van Dissel, PhD, MD	LUMC
Principal Investigator:	T W Kuijpers, PhD, MD	AIDS Malignancy Clinical Trials Consortium
Principal Investigator:	E AM Sanders, PhD, MD	UMCU

More Information

No publications provided

Responsible Party:	J.T. van Dissel, LUMC
ClinicalTrials.gov Identifier:	NCT00522821 History of Changes
Other Study ID Numbers:	IUWP2005.01
Study First Received:	August 29, 2007
Last Updated:	July 19, 2011
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Sanquin:

IgG subclass deficiency
Anti-polysaccharide deficiency
therapy
Immunoglobulins, Intravenous
co-trimoxazole

Additional relevant MeSH terms:

IgG Deficiency
Dysgammaglobulinemia
Blood Protein Disorders
Hematologic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Antibodies
Immunoglobulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Trimethoprim-Sulfamethoxazole Combination

Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Infective Agents, Urinary
Anti-Infective Agents
Therapeutic Uses
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on February 09, 2012