Effect of Albendazole Dose on Treatment of Lymphatic Filariasis

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00511004
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 3
• Duration (Months): 79.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This study is conducted in Kerala, India. It will determine whether a new treatment regimen of albendazole and diethylcarbamazine (DEC) for lymphatic filariasis can eliminate the disease more quickly than the standard regimen. Lymphatic filariasis is caused by infection with very small parasitic worms that are spread by mosquitoes. The disease can cause swelling of the arms, legs, breast and scrotum and can progress to permanent swelling of the legs or arms called elephantiasis. The study will see if a higher and more frequent dose of albendazole is better at clearing filarial worms from the blood than the current treatment.

Healthy people between 18 and 55 years of age who are in good health and who are infected with filarial worms may be eligible for this study.

Participants undergo the following procedures:

3-day hospital stay at the Filariasis Chemotherapy Unit of the T.D. Medical College Hospital in Kerala, India

• Random assignment to receive either: 400 mg albendazole and DEC 300 mg given once a year for 2 years (standard treatment); or 800 mg albendazole and DEC 300 mg given once a year for 2 years; or 800 mg albendazole and DEC 300 mg given twice a year for 2 years.

• Urine pregnancy test for women of childbearing age .

• Ultrasound test to look for filarial worms.

• Treatment dose.

• Monitoring for symptoms

6-month 3-day hospital stay

• Medical history, physical examination and blood test.

• Repeat ultrasound in subjects whose first ultrasound detected adult worms.

• Treatment dose for subjects receiving medicine every 6 months.

• Urine pregnancy test for women of childbearing age.

1-year 3-day hospital stay

• Medical history, physical examination and blood test.

• Treatment dose.

• Repeat ultrasound in subjects whose first ultrasound detected adult worms.

• Urine pregnancy test for women of childbearing age.

18-month 3-day hospital stay

• Medical history, physical examination and blood test.

• Treatment dose for subjects receiving medicine every 6 months.

• Urine pregnancy test for women of childbearing age.

24-month 3-day hospital stay

• Medical history, physical examination and blood test.

• Treatment dose.

• Repeat ultrasound in subjects whose first ultrasound detected adult worms.

• Urine pregnancy test for women of childbearing age.

Condition or Disease	Intervention/Treatment	Phase
Lymphatic Filariasis	Drug: Albendazole; Drug: Diethylcarbamazine	Phase 2

Detailed Description

Albendazole and diethylcarbamazine (DEC) are currently used in combination for annual mass treatment of lymphatic filariasis in all parts of the world except Africa. Although the drugs have been donated, the cost of such programs is very high and has proven to be a major impediment to the success of programs in many countries with limited financial resources. Data from albendazole treatment of other filarial infections and one study comparing single to multi-dose DEC/albendazole in lymphatic filariasis suggest that increased dose and/or frequency of albendazole dosing may be more effective in clearing microfilariae. In this study, 75 volunteers with microfilaremic Brugia malayi infection will be randomized to receive standard annual therapy (albendazole 400 mg + DEC 300 mg), annual therapy with increased dosing of albendazole (albendazole 800 mg + DEC 300 mg), or semiannual therapy with an increased albendazole dose (albendazole 800 mg + DEC 300 mg). Microfilarial levels will be followed every 6 months for 2 years to determine whether the higher dose, and/or the more frequent regimen, is more effective.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Albendazole Dose and Interval on Brugia Malayi Microfilarial Clearance in India: A Randomized, Open Label Study
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Diethylcarbamazine/Albendazole -STD Standard therapy of DEC (300mg) and albendazole (400mg) yearly	Drug: Albendazole; Comparing 400 mg to 800 mg dose; Other Names: Zentel ; Drug: Diethylcarbamazine; Providing diethylcarbamazine more frequently in combination with albendazole; Other Names: Banocide
Active Comparator: Diethylcarbamazine/Albendazole- HD1 High dose of DEC (300mg) and albendazole (800mg) yearly	Drug: Albendazole; Comparing 400 mg to 800 mg dose; Other Names: Zentel ; Drug: Diethylcarbamazine; Providing diethylcarbamazine more frequently in combination with albendazole; Other Names: Banocide
Active Comparator: Diethylcarbamazine/Albendazole-HD2 High dose of DEC (300mg) and albendazole (800mg) twice yearly (every 6 months)	Drug: Albendazole; Comparing 400 mg to 800 mg dose; Other Names: Zentel ; Drug: Diethylcarbamazine; Providing diethylcarbamazine more frequently in combination with albendazole; Other Names: Banocide

Outcome Measures

Primary Outcome Measures

1. Microfilarial Counts at 1 Year [1 year from time enrolled]

   Night time microfilarial counts at 1 year

Secondary Outcome Measures

1. Adult Worm Burdens at 2 Years [2 years from the time enrolled.]

   Doppler detected worm nests at 2 years

2. Microfilarial Levels at 2 Years [2 years from time enrolled]

   Night time microfilarial levels at 2 years

3. Brugia Specific Immunoglobulin G4 (IgG4) Antibodies [2 years]

   IgG4 antibodies directed against Brugia malayi antigen

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

Inclusion Criteria for Screening:

• Age 18 years to 55 years inclusive

• Both genders

• Not pregnant or breastfeeding by history

• If selected, subjects must be willing to spend 3 days on the Filariasis Chemotherapy Unit at the T.D. Medical College Hospital, Alleppey, Kerala, India

• If selected, subjects must be willing to undergo nighttime blood draws once every 6 months and Doppler ultrasound twice yearly for 2 years

• If selected, agree to have blood stored for future studies

• Ability to understand and give informed consent

Inclusion Criteria for Treatment:

• Age 18 to 55 years inclusive

• Men and non-pregnant or non-breast feeding women

• Microfilarial levels greater than 50mf/mL

• Willingness to spend 3 days on the Filariasis Chemotherapy Unit at the T.D. Medical College Hospital, Alleppey, Kerala, India every 6 months for 2 years

• Willingness to undergo nighttime blood draws once every 6 months for 2 years

• Ability to understand and give informed consent

• Hemaglobin (Hgb) levels for inclusion greater than 9 g/dL

• Creatinine (Cr) less than or equal to 1.2 mg/dL

• Alanine aminotransferase (ALT) less than 30 U/L

• Willingness to have blood stored for future studies

EXCLUSION CRITERIA:

Exclusion Criteria for Screening:

• Age less than 18 years or greater than 55 years

• Pregnant or breast feeding by history

Exclusion Criteria for Treatment:

• Non-volunteers

• Age less than 18 years or greater than 55 years

• Pregnant or breast feeding

• Hgb levels less than or equal to 9 g/dL

• Cr greater than 1.3 mg/dL

• ALT greater than 30 U/L

• Alcohol consumption of more than 2 beers or other alcohol-containing drinks/day within a week of each drug administration

• Temperature greater than 37.5 degrees Celsius

• Serious medical illness

• History of benzimidazole allergy

• History of DEC allergy

• Use of albendazole or DEC within past 6 months

• Unwillingness to comply with required study visits

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Filariasis Chemotherapy Unit (FCU), T.D. Medical Hospital	Alleppey, Kerala		India

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Thomas B Nutman, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Study Documents (Full-Text)

None provided.

More Information

Publications

• Edwards G, Awadzi K, Breckenridge AM, Gilles HM, Orme ML, Ward SA. Diethylcarbamazine disposition in patients with onchocerciasis. Clin Pharmacol Ther. 1981 Oct;30(4):551-7.
• Partono F, Purnomo, Oemijati S, Soewarta A. The long term effects of repeated diethylcarbamazine administration with special reference to microfilaraemia and elephantiasis. Acta Trop. 1981 Sep;38(3):217-25.
• Taylor HR, Greene BM. Ocular changes with oral and transepidermal diethylcarbamazine therapy of onchocerciasis. Br J Ophthalmol. 1981 Jul;65(7):494-502.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00511004
• Other Study ID Numbers: 999907197; 07-I-N197
• First Posted: Aug 3, 2007
• Last Update Posted: Aug 31, 2015
• Last Verified: Jul 1, 2015

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Brugia Malayi; Lymphatic Filariasis; Albendazole; Diethylcarbamazine
• Additional relevant MeSH terms: Filariasis; Elephantiasis, Filarial; Elephantiasis; Albendazole; Diethylcarbamazine

Study Results

Participant Flow

Recruitment Details	Adults living in Kerala, India with Brugia malayi microfilaremia were recruited from field sites around the city of Alleppey and the study performed in the outpatient department of the TD Medical College.

Arm/Group Title	Standard Therapy Annual DEC/ALB	High Dose Annual DEC/ALB	High Dose Semiannual DEC/ALB
Arm/Group Description	Group randomized to standard therapy that consists of Annual diethylcarbamazine (300 mg) and albendazole (400mg)	Group randomized to yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)	Group randomized to twice-yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)
Period Title: Overall Study
STARTED	13	13	14
COMPLETED	13	13	10
NOT COMPLETED	0	0	4

Baseline Characteristics

Arm/Group Title	Standard Therapy Annual DEC/ALB	High Dose Annual DEC/ALB	High Dose Semiannual DEC/ALB	Total
Arm/Group Description	Group randomized to standard therapy that consists of Annual diethylcarbamazine (300 mg) and albendazole (400mg)	Group randomized to yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)	Group randomized to twice-yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)	Total of all reporting groups
Overall Participants	13	13	14	40
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	13 100%	13 100%	14 100%	40 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	36	39	37	37
Sex: Female, Male (Count of Participants)
Female	9 69.2%	10 76.9%	10 71.4%	29 72.5%
Male	4 30.8%	3 23.1%	4 28.6%	11 27.5%
Region of Enrollment (participants) [Number]
India	13 100%	13 100%	14 100%	40 100%
Blood microfilaremia (mf/ml) (MF/ML) [Median (Full Range) ]
Median (Full Range) [MF/ML]	412	264	384	384

Outcome Measures

1. Primary Outcome

Title	Microfilarial Counts at 1 Year
Description	Night time microfilarial counts at 1 year
Time Frame	1 year from time enrolled

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Therapy Annual DEC/ALB	High Dose Annual DEC/ALB	High Dose Semiannual DEC/ALB
Arm/Group Description	Group randomized to standard therapy that consists of Annual diethylcarbamazine (300 mg) and albendazole (400mg)	Group randomized to yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)	Group randomized to twice-yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)
Measure Participants	13	13	13
Median (Full Range) [MF/ML]	0	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Therapy Annual DEC/ALB, High Dose Annual DEC/ALB, High Dose Semiannual DEC/ALB
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.2
	Comments	Adjusted for multiple comparisons
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Adult Worm Burdens at 2 Years
Description	Doppler detected worm nests at 2 years
Time Frame	2 years from the time enrolled.

Outcome Measure Data

Analysis Population Description

By 2 years, 4 subjects in High Dose Group lost to followup

Arm/Group Title	Standard Therapy Annual DEC/ALB	High Dose Annual DEC/ALB	High Dose Semiannual DEC/ALB
Arm/Group Description	Group randomized to standard therapy that consists of Annual diethylcarbamazine (300 mg) and albendazole (400mg)	Group randomized to yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)	Group randomized to twice-yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)
Measure Participants	13	13	10
Median (Full Range) [Number of nests]	0	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Therapy Annual DEC/ALB, High Dose Annual DEC/ALB, High Dose Semiannual DEC/ALB
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Microfilarial Levels at 2 Years
Description	Night time microfilarial levels at 2 years
Time Frame	2 years from time enrolled

Outcome Measure Data

Analysis Population Description

By 2 years, 4 subjects in High Dose Group lost to followup

Arm/Group Title	Diethylcarbamazine/Albendazole -STD	Diethylcarbamazine/Albendazole- HD1	Diethylcarbamazine/Albendazole-HD2
Arm/Group Description	Standard therapy of diethylcarbamazine (DEC) (300mg) and albendazole (400mg) yearly Albendazole: Comparing 400 mg to 800 mg dose Diethylcarbamazine: Providing diethylcarbamazine more frequently in combination with albendazole	High dose of DEC (300mg) and albendazole (800mg) yearly Albendazole: Comparing 400 mg to 800 mg dose Diethylcarbamazine: Providing diethylcarbamazine more frequently in combination with albendazole	High dose of DEC (300mg) and albendazole (800mg) twice yearly (every 6 months) Albendazole: Comparing 400 mg to 800 mg dose Diethylcarbamazine: Providing diethylcarbamazine more frequently in combination with albendazole
Measure Participants	13	13	10
Median (Full Range) [MF/ML]	0	0	0

4. Secondary Outcome

Title	Brugia Specific Immunoglobulin G4 (IgG4) Antibodies
Description	IgG4 antibodies directed against Brugia malayi antigen
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

By 2 years, 4 subjects in High Dose Group lost to followup

Arm/Group Title	Standard Therapy Annual DEC/ALB	High Dose Annual DEC/ALB	High Dose Semiannual DEC/ALB
Arm/Group Description	Group randomized to standard therapy that consists of Annual diethylcarbamazine (300 mg) and albendazole (400mg)	Group randomized to yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)	Group randomized to twice-yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)
Measure Participants	13	13	10
Median (Full Range) [ng/ml]	150	224	128

Adverse Events

Time Frame	Every 6 months
Arm/Group Title	Standard Therapy Annual DEC/ALB		High Dose Annual DEC/ALB		High Dose Semiannual DEC/AC=LB
Arm/Group Description	Group randomized to standard therapy that consists of Annual diethylcarbamazine (300 mg) and albendazole (400mg)		Group randomized to yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)		Group randomized to twice-yearly high dose albendazole that consists of Annual diethylcarbamazine (300 mg) and albendazole (800mg)
All Cause Mortality
	Standard Therapy Annual DEC/ALB		High Dose Annual DEC/ALB		High Dose Semiannual DEC/AC=LB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Standard Therapy Annual DEC/ALB		High Dose Annual DEC/ALB		High Dose Semiannual DEC/AC=LB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/13 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Standard Therapy Annual DEC/ALB		High Dose Annual DEC/ALB		High Dose Semiannual DEC/AC=LB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/13 (69.2%)		8/13 (61.5%)		11/14 (78.6%)
Gastrointestinal disorders
Nausea/Vomiting	1/13 (7.7%)	1	1/13 (7.7%)	1	0/14 (0%)	0
Investigations
Fever	5/13 (38.5%)	5	4/13 (30.8%)	4	4/14 (28.6%)	4
Musculoskeletal and connective tissue disorders
Myalgia	9/13 (69.2%)	9	8/13 (61.5%)	8	11/14 (78.6%)	11

Limitations/Caveats

Study never fully enrolled so sample size was smaller than hoped for.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.