PMID- 18425621
OWN - NLM
STAT- MEDLINE
DCOM- 20080701
LR  - 20211020
IS  - 0340-5354 (Print)
IS  - 0340-5354 (Linking)
VI  - 255
IP  - 4
DP  - 2008 Apr
TI  - Thalidomide causes sinus bradycardia in ALS.
PG  - 587-91
LID - 10.1007/s00415-008-0756-3 [doi]
AB  - OBJECTIVE: Neuroinflammation contributes to motor neuron degeneration in ALS. 
      Thalidomide (THL) shows potent anti-inflammatory properties and increased the 
      lifespan in ALS transgenic mice. Thalidomide was therefore suggested as 
      atherapeutic intervention for the treatment of ALS.We conducted a pilot, 
      randomized clinical trial of THL in patients with ALS to assess safety, 
      feasibility, and preliminary estimates of treatment efficacy. METHODS: Patients 
      were randomized to THL in combination with riluzole (n = 18) or riluzole alone (n 
      = 19). THL was initiated at 100 mg per day for 6 weeks. Thereafter, the dose was 
      increased every week by 50 mg until reaching the dose of 400 mg per day and 
      planned to continue for another 12 weeks. RESULTS: Within 12 weeks of THL 
      treatment, nine THL patients (50%) developed bradycardia defined as a heart rate 
      below 60 beats per minute (bpm) and ranged from 46 to 59 bpm. Mean heart rate 
      dropped by 17 bpm with THL treatment. Severe symptomatic bradycardia of 30 bpm 
      occurred in one patient. A further patient died from sudden unexpected death. The 
      study was terminated prematurely for safety concerns. The secondary outcome 
      variables showed similar results for both groups. CONCLUSION: Bradycardia was the 
      most common adverse event of THL treatment in ALS. THL-related bradycardia does 
      not appear to be ALS-specific. It is conceivable, however, that the unexpected 
      frequency and severity of THL-induced bradycardia may be related to subclinical 
      involvement of the autonomic nervous system in ALS. The cardiac toxicity 
      discourages further clinical trials and compassionate use of THL in ALS. 
      ClinicalTrials.gov Identifier: NCT00231140.
FAU - Meyer, Thomas
AU  - Meyer T
AD  - Dept. of Neurology, Charite University Hospital, Campus Virchow-Klinikum, 
      Ambulanz fur ALS und andere Motoneuronenerkrankungen, Augustenburger Platz 1, 
      13353 Berlin, Germany. thomas.meyer@charite.de
FAU - Maier, Andre
AU  - Maier A
FAU - Borisow, Nadja
AU  - Borisow N
FAU - Dullinger, Jorn S
AU  - Dullinger JS
FAU - Splettstosser, Gerald
AU  - Splettstosser G
FAU - Ohlraun, Stephanie
AU  - Ohlraun S
FAU - Munch, Christoph
AU  - Munch C
FAU - Linke, Peter
AU  - Linke P
LA  - eng
SI  - ClinicalTrials.gov/NCT00231140
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20080421
PL  - Germany
TA  - J Neurol
JT  - Journal of neurology
JID - 0423161
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Immunosuppressive Agents)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - 7LJ087RS6F (Riluzole)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Amyotrophic Lateral Sclerosis/complications/*drug therapy/immunology
MH  - Anti-Inflammatory Agents/administration & dosage/adverse effects
MH  - Arrhythmia, Sinus/*chemically induced/physiopathology
MH  - Bradycardia/*chemically induced/physiopathology
MH  - Death, Sudden/etiology
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Drug Therapy, Combination
MH  - Electrocardiography
MH  - Excitatory Amino Acid Antagonists/administration & dosage
MH  - Humans
MH  - Immunosuppressive Agents/administration & dosage/adverse effects
MH  - Inflammation/*drug therapy/immunology
MH  - Middle Aged
MH  - Parasystole/*chemically induced/physiopathology
MH  - Pilot Projects
MH  - Riluzole/administration & dosage
MH  - Thalidomide/administration & dosage/*adverse effects
MH  - Treatment Outcome
EDAT- 2008/04/22 09:00
MHDA- 2008/07/02 09:00
CRDT- 2008/04/22 09:00
PHST- 2007/05/03 00:00 [received]
PHST- 2007/09/27 00:00 [accepted]
PHST- 2007/08/26 00:00 [revised]
PHST- 2008/04/22 09:00 [pubmed]
PHST- 2008/07/02 09:00 [medline]
PHST- 2008/04/22 09:00 [entrez]
AID - 10.1007/s00415-008-0756-3 [doi]
PST - ppublish
SO  - J Neurol. 2008 Apr;255(4):587-91. doi: 10.1007/s00415-008-0756-3. Epub 2008 Apr 
      21.