Difference between revisions of "Plan for an Integral Clinical Trial"

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=== Selection by Trial Results ===
 
=== Selection by Trial Results ===
  
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[[Acetyl L-carnitine (ALCAR)]] {{#pmid:23421600|beghi2013}}
  
 
=== Selection by Processes ===
 
=== Selection by Processes ===

Revision as of 17:06, 10 August 2017

A number of substances have been trialed individually for ALS, and some of them have shown preliminary results that warrant further studies. Even more of them have a plausible mechanism but no clinical results. Although ALS is a collection of diverse diseases, it is possible to recognize several characteristic parameters or processes, manipulation of which would probably be beneficial to majority of PALS.

The aim of this exercise is to propose a "cocktail" consisting of several substances that can be tested integrally in order to see if they have a combined measurable effect on ALS progression.


Selection of Substances

General Criteria

The substances to be included in the cocktail should either be available as over-tnhe-counter products or prescribing them off label should be straightforward. In addition, they need to fulfil at least one of the following criteria:

  1. preliminary signs of efficacy in a human trial
  2. validated effect on a parameter or process that can be estimated to decelerate disease progression in a majority of ALS patients

Selection by Trial Results

Acetyl L-carnitine (ALCAR) [1]

Selection by Processes

The basis of this section is the page Supplements listed by their effects


Process/Parameter How common in ALS? Effect of Manipulation Candidate Substances
Neuroinflammation General Reduction is probably beneficial; M2 state of microglia should be promoted. 3nB, Baicalin, Curcumin, Ibuprofen, Luteolin,Magnolia bark extract, Peony root extract, Spirulina, Trimethylglycine, Vitamin D3
  1. Beghi et al.: Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for ALS. Amyotroph Lateral Scler Frontotemporal Degener 2013;14:397-405. PMID: 23421600. DOI. Our objective was to assess the effects of acetyl-L-carnitine (ALC) with riluzole on disability and mortality of amyotrophic lateral sclerosis (ALS). Definite/probable ALS patients, 40-70 years of age, duration 6-24 months, self-sufficient (i.e. able to swallow, cut food/handle utensils, and walk), and with forced vital capacity (FVC) > 80% entered a pilot double-blind, placebo-controlled, parallel group trial and were followed for 48 weeks. ALC or placebo 3 g/day was added to riluzole 100 mg/day. Primary endpoint: number of patients no longer self-sufficient. Secondary endpoints: changes in ALSFRS-R, MRC, FVC and McGill Quality of Life (QoL) scores. Analysis was made in the intention-to-treat (ITT) and per-protocol (PP) population, completers and completers/compliers (i.e. taking > 75% of study drug). Forty-two patients received ALC and 40 placebo. In the ITT population, 34 (80.9%) patients receiving ALC and 39 (97.5%) receiving placebo became non-self-sufficient (p = 0.0296). In the PP analysis, percentages were 84.4 and 100.0% (p = 0.0538), respectively. Mean ALSFRS-R scores at 48 weeks were 33.6 (SD 10.4) and 27.6 (9.9) (p = 0.0388), respectively, and mean FVC scores 90.3 (32.6) and 58.6 (31.2) (p = 0.0158), respectively. Median survival was 45 months (ALC) and 22 months (placebo) (p = 0.0176). MRC, QoL and adverse events were similar. In conclusion, ALC may be effective, well-tolerated and safe in ALS. A pivotal phase III trial is needed.