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.
RCT Entities:
OBJECTIVE: Neuroinflammation contributes to motor neuron degeneration in ALS. Thalidomide (THL) shows potent anti-inflammatory properties and increased the lifespan in ALStransgenic 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 THLpatients (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.
Authors: P Kaufmann; G Levy; J L P Thompson; M L Delbene; V Battista; P H Gordon; L P Rowland; B Levin; H Mitsumoto Journal: Neurology Date: 2005-01-11 Impact factor: 9.910
Authors: Elijah W Stommel; Jeffrey A Cohen; Camilo E Fadul; Christopher H Cogbill; David J Graber; Linda Kingman; Todd Mackenzie; Jacqueline Y Channon Smith; Brent T Harris Journal: Amyotroph Lateral Scler Date: 2009 Oct-Dec
Authors: Charis Wong; Maria Stavrou; Elizabeth Elliott; Jenna M Gregory; Nigel Leigh; Ashwin A Pinto; Timothy L Williams; Jeremy Chataway; Robert Swingler; Mahesh K B Parmar; Nigel Stallard; Christopher J Weir; Richard A Parker; Amina Chaouch; Hisham Hamdalla; John Ealing; George Gorrie; Ian Morrison; Callum Duncan; Peter Connelly; Francisco Javier Carod-Artal; Richard Davenport; Pablo Garcia Reitboeck; Aleksandar Radunovic; Venkataramanan Srinivasan; Jenny Preston; Arpan R Mehta; Danielle Leighton; Stella Glasmacher; Emily Beswick; Jill Williamson; Amy Stenson; Christine Weaver; Judith Newton; Dawn Lyle; Rachel Dakin; Malcolm Macleod; Suvankar Pal; Siddharthan Chandran Journal: Brain Commun Date: 2021-10-23
Authors: André Maier; Nikolaus Deigendesch; Kathrin Müller; Jochen H Weishaupt; Alexander Krannich; Robert Röhle; Felix Meissner; Kaaweh Molawi; Christoph Münch; Teresa Holm; Robert Meyer; Thomas Meyer; Arturo Zychlinsky Journal: PLoS One Date: 2015-10-07 Impact factor: 3.240