Study design:

Preclinical studies: Efficacy and toxicological studies on lactic acid (LA)-induced sclerozation in pig lumbar discs. Clinical study: Prospective, randomised, double-blinded, placebo-controlled, single ascending dose study investigating the safety and local tolerability of LA.

Objective:

To determine if LA produces sclerozation of the porcine NP followed by a phase Ib study to evaluate preliminary safety, tolerability and efficacy of LA in patients with chronic discogenic low back pain.

Summary of background data:

Surgical stabilization of a motion segment harboring a painful degenerated disc often affords symptomatic relief. In the present study, the hypothesis was tested that LA can produce sclerozation and stabilization of the nucleus pulposus (NP).

Methods:

LA (0.2 mL; 60, 120 or 240 mg/mL) or vehicle was injected into the NP or close to the extra spinal region of spinal nerves of young female pigs. The size of the NP, MRI changes, flexural stiffness and histology of the disc was studied after up to 84 days of survival. Fifteen patients injected intra discally with placebo (iohexol, 1.5 mL, n = 6) or iohexol plus LA (30, 60 or 120 mg/mL; 3 patients in each group) were followed for up to 12 months.

Results:

Injection of LA in the pig reproducibly induced sclerozation of the NP and increased flexural rigidity. Histological changes included generation of connective tissue and increased expression of collagen I. No safety concerns were raised. Adverse events in patients were limited to transiently increased low back pain with no obvious difference between treatment groups. There was indication of lower water content of NP injected with the 2 highest doses of LA.

Conclusions:

LA has a sclerozing effect on the NP in pigs and patients and is therefore a candidate for further clinical studies powered to determine its potential as a treatment of chronic discogenic low back pain.

Level of evidence:

2.