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Thalidomide for Treatment of Oral and Esophageal Aphthous Ulcers and HIV Viremia in Patients With HIV Infection

Primary Purpose

HIV Infections, Stomatitis, Aphthous

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Thalidomide
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Thalidomide, Stomatitis, Aphthous

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Concurrent Medication: Allowed: Anti-HIV therapy provided therapy has remained constant in the 4 weeks prior to study entry. Narcotic analgesia after the first week of treatment ONLY IF the patient is not experiencing somnolence. Patients must have: Documented HIV infection or AIDS. Biopsy-confirmed aphthous ulceration of the mouth or esophagus lasting at least 2 weeks. Negative culture of ulcer for Herpes simplex. En face diameter of >= 5 mm for largest aphthous ulcer. Life expectancy of at least 3 months. NOTE: This study is approved for prisoner participation. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Known allergy to thalidomide. Grade 2 or worse bilateral peripheral neuropathy. EXCLUDED FOR MAINTENANCE PHASE: Toxicity other than somnolence in acute phase that required discontinuation of drug. Concurrent Medication: Excluded: Acute therapy for opportunistic infection. ddC. Pentoxifylline. Methotrexate, trimetrexate, antineoplastic alkylating agents. Other putative immunomodulators. CNS depressants and/or medications with sedative or hypnotic effect. Systemic and/or oral topical corticosteroids. Systemic chemotherapy for Kaposi's sarcoma or other malignancies. Compounded antibacterial mouthwashes containing anti-infective agents (such as doxycycline, minocycline, tetracycline, or nystatin). Concurrent Treatment: Excluded: Radiation to head and/or neck. Patients with the following prior conditions are excluded: History of grade 2 or worse bilateral peripheral neuropathy. Change in anti-HIV therapy within 4 weeks prior to study entry. Prior enrollment in ACTG 251 or prior treatment of aphthous ulcers with thalidomide. Prior Medication: Excluded: Systemic and/or oral topical corticosteroids within 1 week prior to first set of bloods drawn. Other putative immunomodulators within 2 weeks prior to study entry. Prior thalidomide for aphthous ulcers.

Sites / Locations

  • Univ of Alabama at Birmingham
  • Univ of Southern California / LA County USC Med Ctr
  • San Francisco AIDS Clinic / San Francisco Gen Hosp
  • Stanford at Kaiser / Kaiser Permanente Med Ctr
  • Harbor UCLA Med Ctr
  • Univ of Colorado Health Sciences Ctr
  • Howard Univ
  • Univ of Miami School of Medicine
  • Queens Med Ctr
  • Univ of Hawaii
  • Northwestern Univ Med School
  • Cook County Hosp
  • Rush Presbyterian - Saint Luke's Med Ctr
  • Louis A Weiss Memorial Hosp
  • Illinois Masonic Med Ctr
  • Indiana Univ Hosp
  • Harvard (Massachusetts Gen Hosp)
  • Beth Israel Deaconess - West Campus
  • Bronx Municipal Hosp Ctr/Jacobi Med Ctr
  • Comprehensive Health Care Ctr / Bronx Municipal Hosp
  • Montefiore Adolescent AIDS Prog / Bronx Municipal Hosp
  • Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
  • Montefiore Family Health Ctr / Bronx Municipal Hosp
  • Jack Weiler Hosp / Bronx Municipal Hosp
  • Montefiore Med Ctr / Bronx Municipal Hosp
  • North Central Bronx Hosp / Bronx Municipal Hosp
  • Bronx Veterans Administration / Mount Sinai Hosp
  • SUNY / Erie County Med Ctr at Buffalo
  • Beth Israel Med Ctr
  • Bellevue Hosp / New York Univ Med Ctr
  • Mount Sinai Med Ctr / Pediatrics
  • Mount Sinai Med Ctr
  • SUNY / State Univ of New York
  • Univ of North Carolina
  • Case Western Reserve Univ
  • Milton S Hershey Med Ctr
  • Thomas Jefferson Univ Hosp
  • Meharry Med College
  • Univ of Washington
  • Univ of Puerto Rico

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 27, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Andrulis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00000790
Brief Title
Thalidomide for Treatment of Oral and Esophageal Aphthous Ulcers and HIV Viremia in Patients With HIV Infection
Official Title
Thalidomide for Treatment of Oral and Esophageal Aphthous Ulcers and HIV Viremia in Patients With HIV Infection
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
October 1998 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Andrulis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary
PRIMARY: To evaluate the effectiveness and safety of thalidomide for treatment of oral and esophageal aphthous ulcers (those unrelated to a known infection or malignancy) in patients with advanced HIV disease. To evaluate the effect of thalidomide on HIV load in this patient population. Per 06/28/94 amendment, to evaluate the effectiveness of thalidomide in preventing recurrences in patients whose aphthae completely heal at the end of acute treatment. SECONDARY: To evaluate the effect of thalidomide on blood tumor necrosis factor (TNF) levels and to obtain pharmacokinetic data on the drug. Per 06/28/94 amendment, to evaluate the safety of thalidomide. Per 05/10/95 amendment, to explore in a substudy the effects of thalidomide on idiopathic genital aphthous ulcers in HIV-infected women. Aphthous ulcers of the mouth or esophagus can interfere with eating, resulting in malnutrition and wasting. Thalidomide has been proposed as an effective therapy for severe forms of aphthous ulceration in AIDS patients.
Detailed Description
Aphthous ulcers of the mouth or esophagus can interfere with eating, resulting in malnutrition and wasting. Thalidomide has been proposed as an effective therapy for severe forms of aphthous ulceration in AIDS patients. Patients are randomized to receive 4 weeks of either thalidomide or placebo orally, administered once daily. Patients are followed weekly. Complete responders after 4 weeks of acute treatment enter a 24-week maintenance phase. A pharmacokinetic substudy will be included.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Stomatitis, Aphthous
Keywords
Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Thalidomide, Stomatitis, Aphthous

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Enrollment
164 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Thalidomide

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Concurrent Medication: Allowed: Anti-HIV therapy provided therapy has remained constant in the 4 weeks prior to study entry. Narcotic analgesia after the first week of treatment ONLY IF the patient is not experiencing somnolence. Patients must have: Documented HIV infection or AIDS. Biopsy-confirmed aphthous ulceration of the mouth or esophagus lasting at least 2 weeks. Negative culture of ulcer for Herpes simplex. En face diameter of >= 5 mm for largest aphthous ulcer. Life expectancy of at least 3 months. NOTE: This study is approved for prisoner participation. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Known allergy to thalidomide. Grade 2 or worse bilateral peripheral neuropathy. EXCLUDED FOR MAINTENANCE PHASE: Toxicity other than somnolence in acute phase that required discontinuation of drug. Concurrent Medication: Excluded: Acute therapy for opportunistic infection. ddC. Pentoxifylline. Methotrexate, trimetrexate, antineoplastic alkylating agents. Other putative immunomodulators. CNS depressants and/or medications with sedative or hypnotic effect. Systemic and/or oral topical corticosteroids. Systemic chemotherapy for Kaposi's sarcoma or other malignancies. Compounded antibacterial mouthwashes containing anti-infective agents (such as doxycycline, minocycline, tetracycline, or nystatin). Concurrent Treatment: Excluded: Radiation to head and/or neck. Patients with the following prior conditions are excluded: History of grade 2 or worse bilateral peripheral neuropathy. Change in anti-HIV therapy within 4 weeks prior to study entry. Prior enrollment in ACTG 251 or prior treatment of aphthous ulcers with thalidomide. Prior Medication: Excluded: Systemic and/or oral topical corticosteroids within 1 week prior to first set of bloods drawn. Other putative immunomodulators within 2 weeks prior to study entry. Prior thalidomide for aphthous ulcers.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacobson JM
Official's Role
Study Chair
Facility Information:
Facility Name
Univ of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Univ of Southern California / LA County USC Med Ctr
City
Los Angeles
State/Province
California
ZIP/Postal Code
900331079
Country
United States
Facility Name
San Francisco AIDS Clinic / San Francisco Gen Hosp
City
San Francisco
State/Province
California
ZIP/Postal Code
941102859
Country
United States
Facility Name
Stanford at Kaiser / Kaiser Permanente Med Ctr
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Harbor UCLA Med Ctr
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
Univ of Colorado Health Sciences Ctr
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
Howard Univ
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20059
Country
United States
Facility Name
Univ of Miami School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
331361013
Country
United States
Facility Name
Queens Med Ctr
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96816
Country
United States
Facility Name
Univ of Hawaii
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96816
Country
United States
Facility Name
Northwestern Univ Med School
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Cook County Hosp
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Rush Presbyterian - Saint Luke's Med Ctr
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Louis A Weiss Memorial Hosp
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60640
Country
United States
Facility Name
Illinois Masonic Med Ctr
City
Chicago
State/Province
Illinois
ZIP/Postal Code
606575147
Country
United States
Facility Name
Indiana Univ Hosp
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
462025250
Country
United States
Facility Name
Harvard (Massachusetts Gen Hosp)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess - West Campus
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Comprehensive Health Care Ctr / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Montefiore Adolescent AIDS Prog / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Montefiore Family Health Ctr / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Jack Weiler Hosp / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10465
Country
United States
Facility Name
Montefiore Med Ctr / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
North Central Bronx Hosp / Bronx Municipal Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Bronx Veterans Administration / Mount Sinai Hosp
City
Bronx
State/Province
New York
ZIP/Postal Code
10468
Country
United States
Facility Name
SUNY / Erie County Med Ctr at Buffalo
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
Beth Israel Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Bellevue Hosp / New York Univ Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Mount Sinai Med Ctr / Pediatrics
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Mount Sinai Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
SUNY / State Univ of New York
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Univ of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
275997215
Country
United States
Facility Name
Case Western Reserve Univ
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Milton S Hershey Med Ctr
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
170330850
Country
United States
Facility Name
Thomas Jefferson Univ Hosp
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
191075098
Country
United States
Facility Name
Meharry Med College
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Univ of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
981224304
Country
United States
Facility Name
Univ of Puerto Rico
City
San Juan
ZIP/Postal Code
009365067
Country
Puerto Rico

12. IPD Sharing Statement

Citations:
PubMed Identifier
10353862
Citation
Jacobson JM, Spritzler J, Fox L, Fahey JL, Jackson JB, Chernoff M, Wohl DA, Wu AW, Hooton TM, Sha BE, Shikuma CM, MacPhail LA, Simpson DM, Trapnell CB, Basgoz N. Thalidomide for the treatment of esophageal aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group. J Infect Dis. 1999 Jul;180(1):61-7. doi: 10.1086/314834.
Results Reference
background
PubMed Identifier
9154767
Citation
Jacobson JM, Greenspan JS, Spritzler J, Ketter N, Fahey JL, Jackson JB, Fox L, Chernoff M, Wu AW, MacPhail LA, Vasquez GJ, Wohl DA. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med. 1997 May 22;336(21):1487-93. doi: 10.1056/NEJM199705223362103.
Results Reference
background
PubMed Identifier
11362988
Citation
Gilden D. Thalidomide and aphthous ulcers. GMHC Treat Issues. 1995 Nov;9(11):12.
Results Reference
background
PubMed Identifier
11120935
Citation
Jacobson JM, Greenspan JS, Spritzler J, Fox L, Fahey JL, Jackson JB, Chernoff M, Wohl DA, Pulvirenti JJ, Hooton TM, Shikuma C. Thalidomide in low intermittent doses does not prevent recurrence of human immunodeficiency virus-associated aphthous ulcers. J Infect Dis. 2001 Jan 15;183(2):343-346. doi: 10.1086/317928. Epub 2000 Dec 15.
Results Reference
background
PubMed Identifier
11583477
Citation
Aweeka F, Trapnell C, Chernoff M, Jayewardene A, Spritzler J, Bellibas SE, Lizak P, Jacobson J. Pharmacokinetics and pharmacodynamics of thalidomide in HIV patients treated for oral aphthous ulcers: ACTG protocol 251. AIDS Clinical Trials Group. J Clin Pharmacol. 2001 Oct;41(10):1091-7. doi: 10.1177/00912700122012698.
Results Reference
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Thalidomide for Treatment of Oral and Esophageal Aphthous Ulcers and HIV Viremia in Patients With HIV Infection

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