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

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.

4.0 TREATMENT PLAN

4.1 Pretreatment measurements will include:

1. 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. 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.
2. Complete physical examination.
3. Blood draw at initiation of hemodialysis session for CRP, IL-6, albumin, prealbumin and α1 acid glycoprotein ( α1 AG).
4. Instruction on birth control methods required.
5. Randomization to thalidomide or no treatment control group.

4.2 Detailed description of treatment

A total of 24 subjects will be studied; 12 will receive no drug and 12 will receive thalidomide. Subjects randomized to receive thalidomide will be given 100 mg (two 50 mg active capsules) to take HS. Subjects will have blood drawn weekly during the first 4 weeks. At each of these visits, the patients who are in the active drug arm will undergo a capsule count to establish a compliance range of > 85%. 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 and followed for an additional 4 weeks. Subjects who are compliant within 85% of medication and are fully compliant with birth control measures will be further studied.

At the end of the 4th week, drug subjects will again be examined with special attention to skin and evaluation of peripheral nervous system for a change in or appearance of sensory neuropathy. Compliance will again be assessed.

If somnolence is tolerable (subjects do not have residual somnolence in the morning) the dose will be increased to 200 mg (4 capsules). Blood will be drawn again on the 8th week and the patient will be examined again with attention to the skin and peripheral nervous system. Compliance with both contraceptive requirements and with regard to drug use will be established at each visit. Blood will be drawn every 4 weeks after the start of drug for a total of 24 weeks from initiation of drug. Subjects will have a limited physical examination monthly after the first month.

Patients will remain on study for an additional 4 weeks and will have final evaluation at week 28 which will include a blood draw.

• Experimental: Treatment
  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. Patients will receive Thalidomide for a period of 24 weeks.
  5. Blood will be drawn every 4 weeks for a total of 28 weeks to establish the effect on albumin, prealbumin and CRP
  Intervention: Drug: thalidomide
• Sham Comparator: Control
  This arm will consist of 12 hemodialysis patients having elevated CRP and low albumin levels (less than 3.8 by BCG) who will be treated with a placebo for 24 weeks. Blood will be drawn every 4 weeks for measurement of CRP, albumin and prealbumin
  Intervention: Drug: thalidomide

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.