Randomized Study of Folic Acid Therapy for Hyperhomocysteinemia in Patients With End Stage Renal Disease Receiving Hemodialysis

PROTOCOL OUTLINE: This is a randomized, placebo controlled study. Patients are stratified
according to prestudy homocysteine levels (above or below average). Patients are randomized
to receive placebo or one of two doses of oral folic acid, with or without pyridoxine and
cyanocobalamin.

Arm I: Patients receive oral placebo daily. Arm II: Patients receive oral pyridoxine,
cyanocobalamin, and oral placebo daily.

Arm III: Patients receive oral pyridoxine, cyanocobalamin, and folic acid daily.

Arm IV: Patients receive oral pyridoxine and cyanocobalamin plus a higher dose of folic
acid daily.

Arm V: Patients receive oral placebo and oral folic acid daily. Arm VI: Patients receive
oral placebo and higher dose folic acid daily. Treatment continues for 8 weeks.

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

- Diagnosis of end stage renal disease requiring regular hemodialysis treatment 3 times
weekly

- Baseline predialysis total homocysteine concentration in plasma greater than 16
micromoles/L

- No prior or concurrent pernicious anemia

- No blood smear examination showing unexplained macrocytosis

--Prior/Concurrent Therapy--

- Chemotherapy: No concurrent chemotherapy for cancer

- Other: No concurrent levodopa or carbidopa No concurrent penicillamine or
trimethoprim-sulfonamide combination No concurrent antiviral therapy No concurrent
anticonvulsants

--Patient Characteristics--

- Hematopoietic: Hematocrit at least 25%

- Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use
effective contraception No Parkinson's disease No convulsions or epilepsy requiring
treatment No lactose intolerance or allergy to milk products No history of allergic
sensitization following administration of folic acid, pyridoxine (vitamin B6), or
cyanocobalamin (vitamin B12) No vitamin B12 concentration below lower limit of normal
(150 picamole/L) No untreated hypothyroidism or psoriasis