title: Randomized, placebo-controlled trials of dichlorphenamide in periodic paralysis.
abstract: OBJECTIVE
  To determine the short-term and long-term effects of dichlorphenamide (DCP) on attack frequency and quality of life in hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis.
  
  
  METHODS
  Two multicenter randomized, double-blind, placebo-controlled trials lasted 9 weeks (Class I evidence), followed by a 1-year extension phase in which all participants received DCP. Forty-four HOP and 21 HYP participants participated. The primary outcome variable was the average number of attacks per week over the final 8 weeks of the double-blind phase.
  
  
  RESULTS
  The median attack rate was lower in HOP participants on DCP than in participants on placebo (0.3 vs 2.4, p = 0.02). The 9-week mean change in the Physical Component Summary score of the Short Form-36 was also better in HOP participants receiving DCP (treatment effect = 7.29 points, 95% confidence interval 2.26 to 12.32, p = 0.006). The median attack rate was also lower in HYP participants on DCP (0.9 vs 4.8) than in participants on placebo, but the difference in median attack rate was not significant (p = 0.10). There were no significant effects of DCP on muscle strength or muscle mass in either trial. The most common adverse events in both trials were paresthesia (47% DCP vs 14% placebo, both trials combined) and confusion (19% DCP vs 7% placebo, both trials combined).
  
  
  CONCLUSIONS
  DCP is effective in reducing the attack frequency, is safe, and improves quality of life in HOP periodic paralysis.
  
  
  METHODS
  These studies provide Class I evidence that DCP significantly reduces attack frequency in HOP but lacked the precision to support either efficacy or lack of efficacy of DCP in HYP.
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD. valeria.sansone@unimi.it.
authors: Valeria A
authors: VA
authors: Sansone
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: James
authors: J
authors: Burge
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Michael P
authors: MP
authors: McDermott
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Patty C
authors: PC
authors: Smith
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Barbara
authors: B
authors: Herr
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Rabi
authors: R
authors: Tawil
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Shree
authors: S
authors: Pandya
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: John
authors: J
authors: Kissel
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Emma
authors: E
authors: Ciafaloni
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Perry
authors: P
authors: Shieh
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Jeffrey W
authors: JW
authors: Ralph
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Antony
authors: A
authors: Amato
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Steve C
authors: SC
authors: Cannon
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Jaya
authors: J
authors: Trivedi
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Richard
authors: R
authors: Barohn
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Brian
authors: B
authors: Crum
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Hiroshi
authors: H
authors: Mitsumoto
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Alan
authors: A
authors: Pestronk
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Giovanni
authors: G
authors: Meola
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Robin
authors: R
authors: Conwit
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Michael G
authors: MG
authors: Hanna
authors: From NEMO Clinical Center (V.A.S.) and IRCCS Policlinico San Donato (G.M.), University of Milan, Italy; MRC Centre for Neuromuscular Diseases (J.B., M.G.H.), UCL Institute of Neurology, Queen Square, London, UK; University of Rochester (M.P.M., P.C.S., B.H., R.T., S.P., E.C., R.C.G.), NY; Ohio State University (J.K.), Columbus; UCLA Medical Center (P.S.), Los Angeles, CA; University of California San Francisco School of Medicine (J.W.R.); Brigham and Women's Hospital (A.A.), Boston, MA; UT Southwestern Medical Center (S.C.C., J.T.), Dallas, TX; University of Kansas Medical Center (R.B.), Kansas City; Mayo Clinic (B.C.), Rochester MN; Columbia University (H.M.), New York, NY; Washington University (A.P.), St. Louis, MO; and the Office of Clinical Research (R.C.), NINDS, Bethesda, MD.
authors: Robert C
authors: RC
authors: Griggs
mesh_terms: D000328:Adult; D002257:Carbonic Anhydrase Inhibitors / Q000627:therapeutic use*; D004005:Dichlorphenamide / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010245:Paralyses, Familial Periodic / Q000175:diagnosis* / Q000188:drug therapy*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D004005:Dichlorphenamide