The Effect of Thalidomide in Suppression of the Systemic Inflammatory Response Syndrome in Hemodialysis Patients (ICM)

Phase 3 Study: The Effect of Thalidomide in Suppression of the Systemic Inflammatory Response Syndrome in Hemodialysis Patients

Both malnutrition and inflammation are associated with death in dialysis patients and also with cardiovascular disease. The researchers are testing the idea that inflammation causes malnutrition by using a drug to suppress inflammation in hemodialysis patients to find out whether that will increase blood tests that are associated with malnutrition. The researchers will give hemodialysis patients who have both inflammation and malnutrition either thalidomide or a placebo and compare the effects of treatment on the levels of two proteins in the blood, albumin and prealbumin, that are normally reduced in malnourished patients. Patients who have a serum albumin concentration < 3.8 g/dl will be asked to sign consent to have blood drawn prior to dialysis for measurement of CRP (C-reactive protein). Those with CRP values ≥ 0.8 mg/dl will have a second measurement of CRP performed within 2 weeks. Those with two consecutive values of CRP ≥ 0.8 mg/dl will be eligible for enrollment

Study Overview

• Status: Terminated
• Conditions: Hypoalbuminemia
• Intervention / Treatment: Drug: Thalidomide; Other: Sugar pill

Detailed Description

4.1 Pre-assignment measurements will include:

1. Patient is eligible for enrollment.
2. Complete physical examination.
3. Blood draw at initiation of hemodialysis session
4. Instruction on birth control methods required.
5. Subjects who are non-compliant with regard to medication compliance range or birth control requirements as outlined in the S.T.E.P.S.® program will be immediately discontinued from the study

4.2 Detailed description of treatment: Patients who completed the first 4 weeks will be randomized into Treatment group. A total of 24 subjects will be studied; 12 will receive no drug and 12 will receive thalidomide. Subjects randomized to "Active" Treatment arm will receive Placebo (no-drug/sugar pill) ,or thalidomide 100 mg (two 50 mg active capsules) to take at bedtime. Weekly, Subjects will have blood drawn; will undergo a capsule count to establish a compliance range of > 85%; will have physical exam with special attention to skin and evaluation of peripheral nervous system for a change in or appearance of sensory neuropathy.

If somnolence is tolerable (subjects do not have residual somnolence in the morning) the dose will be increased to 200 mg (4 capsules).

Patients who completed 24 weeks of study will have final evaluation at week 28.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10003
      • Beth Israel Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. End stage renal disease (ESRD) patients on hemodialysis for at least 3 months.
2. Serum C reactive protein level of ≥ 0.8 mg/dl.
3. Serum albumin < 3.8 g/dl (BCG).
4. Signing a written informed consent form.
5. Willingness and ability to comply with the FDA-mandated S.T.E.P.S ® program.
6. Age > 18 years.

Exclusion Criteria:

1. Pregnant and/ or lactating female.
2. Active infection within the previous 8 weeks requiring administration of antibiotics.
3. Patients receiving systemic immunosuppressive therapy.
4. Patients with HIV.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Thalidomide; 12 End stage renal disease (ESRD) patients on hemodialysis for at least 3 months; Serum C reactive protein level of ≥ 0.8 mg/dl; Serum albumin < 3.8 g/dl (BCG); Patients will receive 100mg Thalidomide for a period of 4 weeks; if somnolence tolerated, dosage is increased to 200mg nightly for a period of 20 more weeks -- to total of 24 weeks on Thalidomide.	Drug: Thalidomide; Thalidomide by mouth at night for a total of 24 weeks
PLACEBO_COMPARATOR: No Drug; 12 End stage renal disease (ESRD) patients on hemodialysis for at least 3 months; Serum C reactive protein level of ≥ 0.8 mg/dl; Serum albumin < 3.8 g/dl (BCG); Patients will receive Placebo (Sugar pill) for a period of 24 weeks.	Other: Sugar pill; Placebo by mouth at night for a total of 24 weeks; Other Names: Placebo (no drug)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Serum Albumin	Serum albumin in treated patient and control ("no drug") patients were tabulated once weekly for week #1-4 , then once every 4 weeks thereafter at week# 8, 12, 16, 20, 24 to see changes of health status. Final data collected at week 28 -- to ensure patient safety	28 weeks total
Difference in Serum CRP	Serum CRP in treated patient and control ("no drug") patients were tabulated once weekly for week #1-4 , then once every 4 weeks thereafter at week# 8, 12, 16, 20, 24 to see changes of health status. Final data collected at week 28 -- to ensure patient safety	28 weeks total
Difference in Serum Prealbumin	Serum Prealbumin in treated patient and control ("no drug") patients were tabulated once weekly for week #1-4 , then once every 4 weeks thereafter at week# 8, 12, 16, 20, 24 to see changes of health status. Final data collected at week 28 -- to ensure patient safety	28 weeks total

Collaborators and Investigators

• Sponsor: George A. Kaysen, M.D.
• Collaborators: Beth Israel Medical Center
• Investigators: Principal Investigator: George A Kaysen, MD Ph.D, University of California, Davis; Study Director: James F. Winchester, MD, Beth Israel Medicial Center New York New York

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (ACTUAL): December 1, 2008
• Study Completion (ACTUAL): December 1, 2009

Study Registration Dates

• First Submitted: September 12, 2007
• First Submitted That Met QC Criteria: September 12, 2007
• First Posted (ESTIMATE): September 14, 2007

Study Record Updates

• Last Update Posted (ACTUAL): April 2, 2018
• Last Update Submitted That Met QC Criteria: March 6, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Inflammation; albumin
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Hematologic Diseases; Blood Protein Disorders; Shock; Hypoproteinemia; Systemic Inflammatory Response Syndrome; Hypoalbuminemia; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Thalidomide
• Other Study ID Numbers: 200614929

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO