Phase I clinical trial of safety of L-serine for ALS patients

Figures & data

Figure 1. ALSFRS-R uncorrected slope comparison by dose.

Table I. Baseline comparisons.

Baseline comparisons	Means		Standard deviations
Measure	Placebo	L-serine	Placebo	L-serine		p-value for difference
Initial ALSFRS-R	37.6	39.4	7.38	5.27	0.18
Initial FVC %	90	84	17	19	0.20
Symptom duration (yrs)	1.69	1.36	0.82	0.98	0.16

Table II. ALSFRS-R slope estimates for different statistical models.

Method/Group	Slope (per mo decline)	95% CI	p-value for L-serine effect	ALSFRS-R slope reduction
Separate Fits
Placebo	1.09	(1.01,1.17)
L-serine	0.76	(0.32,1.20)	0.14	30%
Linear mixed effects models uncorrected
Placebo	1.06	(0.98,1.14)
L-serine	0.73	(0.33,1.13)	0.12	31%
Corrected for initial FVC and symptom duration
Placebo	1.16	(1.07,1.25)	0.044	34%
L-serine	0.76	(0.38,1.41)
Corrected and with dose^1
Linear dose effect^2	0.06		0.011
Separate dose effect^3
0.5 g	0.16	(-0.60,0.92)	0.68	14%
2.5 g	0.25	(-0.46,0.96)	0.49	22%
7.5 g	0.25	(-0.53,1.03)	0.53	22%
15.0 g	0.99	(0.20,1.78)	0.014	85%

¹Dose in grams given twice daily.

² Estimate is per gram reduction in slope of ALSFRS-R.

³ Estimates are reductions in slope at the specified dose.

Table III. Increasing L-serine dose increases L-serine biospecimen concentrations.

		Median L-serine concentrations nmoles/ml in end of study samples
Biospecimen type	n	0.5 g BID*	2.5 g BID	7.5 g BID	15.0 g BID
Plasma	12	215	259	435	1464
Urine	12	356	682	1142	2395
CSF	9	36	44	46	137

* BID: twice daily.