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

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

Genetics Home Reference related topics:

aceruloplasminemia

ChemIDplus related topics:

Folic acid Globulin, Immune Immunoglobulins Sulfamethoxazole Trimethoprim Trimethoprim-sulfamethoxazole combination

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Uncontrolled, Crossover Assignment, Safety/Efficacy Study

Official Title:	Treatment in Patients With Recurrent Infections and IgG Subclass Deficiency, and/or Deficient Anti-Polysaccharide Antibody Response

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:	May 2012
Estimated Primary Completion Date:	May 2011 (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 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 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
	AZM	Recruiting
	Maastricht, Netherlands
	Contact: J W Cohen Tervaert, PhD, MD
	Principal Investigator: J W Cohen Tervaert, PhD, MD
	Erasmus MC	Not yet 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
	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
	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
	Jeroen Bosch Ziekenhuis	Not yet recruiting
	Den Bosch, Netherlands
	Contact: E de Vries, PhD,MD
	Principal Investigator: E de Vries, PhD,MD
	UMC St Radboud	Not yet recruiting
	Nijmegen, Netherlands
	Contact: M van Deuren, PhD,MD
	Contact: C RM Weemaes, PhD,MD
	Principal Investigator: M van Deuren, PhD,MD
	Principal Investigator: C RM Weemaes, 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
	VU	Not yet recruiting
	Amsterdam, Netherlands
	Contact: M A van Agtmael, PhD,MD
	Principal Investigator: M van Agtmael
	UMCG	Recruiting
	Groningen, Netherlands
	Contact: C GM Kallenberg, PhD,MD
	Principal Investigator: C GM Kallenberg, PhD,MD

Sponsors and Collaborators

Sanquin

Investigators


Principal Investigator:	J T van Dissel, PhD, MD	LUMC

Principal Investigator:	T W Kuijpers, PhD, MD	AMC

Principal Investigator:	E AM Sanders, PhD, MD	UMCU

More Information

Responsible Party:	LUMC ( J.T. van Dissel )
Study ID Numbers:	IUWP2005.01
First Received:	August 29, 2007
Last Updated:	February 28, 2008
ClinicalTrials.gov Identifier:	NCT00522821
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

Study placed in the following topic categories:

Trimethoprim

Sulfamethoxazole

Blood Protein Disorders

Hematologic Diseases

Trimethoprim-Sulfamethoxazole Combination

Recurrence

Immunologic Deficiency Syndromes

Folic Acid

Antibodies

Immunoglobulins, Intravenous

IgG Deficiency

Rho(D) Immune Globulin

Immunoglobulins

Additional relevant MeSH terms:

Communicable Diseases

Anti-Infective Agents

Antiprotozoal Agents

Immune System Diseases

Immunologic Factors

Physiological Effects of Drugs

Anti-Infective Agents, Urinary

Infection

Renal Agents

Pharmacologic Actions

Antimalarials

Antiparasitic Agents

Therapeutic Uses

Dysgammaglobulinemia

ClinicalTrials.gov processed this record on October 10, 2008

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