24-hour Levodopa-carbidopa Intestinal Gel Lessened Dyskinesia, Parkinson’s Study Finds

24-hour Levodopa-carbidopa Intestinal Gel Lessened Dyskinesia, Parkinson’s Study Finds

A 24-hour treatment with a levodopa-carbidopa intestinal gel (LCIG) lessened the duration and functional effect of dyskinesia — involuntary, jerky movements — in Parkinson’s patients, according to a small study.

The research, “24-hour levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson’s disease,” was published in npj Parkinson’s disease.

Continuous intra-jejunal (the middle part of the small intestine) infusion with a LCIG has been shown to efficiently treat Parkinson’s motor fluctuations. The gel normally is administered with a portable pump directly into the duodenum or upper jejunum by a permanent tube inserted surgically.

Currently, it is mainly used as a 16-hour per day continuous infusion, and is licensed for use in this way. However, additional benefits have been observed when used as a continuous 24-hour infusion in the treatment of severe nocturnal akinesia (losing the ability to move muscles voluntarily), daytime falls and freezing of gait (FOG), as well as poor sleep quality.

Clinical trials have shown that a 16-hour treatment with LCIG can effectively reduce levodopa-induced dyskinesia (LID), which typically occurs after long-term therapy, despite an increase in daily levodopa dose. Current treatments options for LID, such as deep brain stimulation and Gocovri (amantadine, by Adamas Pharmaceuticals) are not uniformly available or are not suitable for all patients.

Researchers from Movement Disorder Unit at Westmead Hospital, in Australia, have now described their clinical experience with a 24-hour LCIG infusion to treat dyskinesia in Parkinson’s patients.

Of 74 patients treated with LCIG for motor fluctuations, 12 (10 men) were treated with 24-hour daily infusion intended to control troublesome daytime dyskinesia and with sufficient data pre- and post- initiation of continuous treatment. Patients’ mean age at the start of 24-hour LCIG was 69 years and mean duration of Parkinson’s was 18 years. Two had a mutation in the PRKN gene, whose mutations are associated with the juvenile form of Parkinson disease.

Among these 12 patients, four took 24-hour LCIG infusion due to lack of response to 16-hour therapy; two due to troublesome dyskinesia and levodopa-unresponsive FOG; three due to levodopa-unresponsive FOG with non-troublesome dyskinesia; two more had troublesome dyskinesia and nocturnal akinesia; and one self-initiated 24-hour therapy. Two transitioned from oral levodopa, without an in-between 16-hour infusion.

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Patients’ clinical characteristics, as well as dyskinesia severity and incidence, were analyzed before and after therapy using the Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) – part 3, part 4 (motor complications) total scores and sub-scores 4.1 (time spent with dyskinesias) and 4.2 (functional impact of dyskinesias). All evaluations were performed at baseline and at six months after starting 16- and 24-hour LCIG.

Daytime dyskinesia was reduced in nine patients (75%) following 24-hour therapy, including seven who were first treated with 16-hour infusion and the two patients who transitioned from oral levodopa.

Of the three patients without decrease in dyskinesia, one could not tolerate 24-hour infusion due to worsening of hallucinations and agitation, and shifted back to 16-hour therapy after two months. After six months, the patient’s neurocognitive function returned to baseline. A second 24-hour therapy was initiated 11 months later, but again led to no benefit. The remaining two patients had no change in dyskinesia despite eased FOG and nocturnal akinesia.

Combining the results from all 12 patients, both the time spent with dyskinesia and its functional impact were reduced during 24-hour LCIG treatment. In contrast, the MDS-UPDRS part 3 “ON” scores — control of motor symptoms — did not change.

Five patients showed lessened dyskinesia despite an overall increase in the total daily levodopa dose. No patient had worsened dyskinesia after a median follow-up of 27.5 months.

A total of three patients had worsening of nocturnal hallucinations, which diminished after lowering the night-time LCIG continuous rate. One patient developed asymptomatic peripheral neuropathy (nerve damage) within six months of 24-hour therapy, which remained stable during 18 months of follow-up.

Ten patients experienced vitamin B6 deficiency requiring supplementation, while seven developed vitamin B12 deficiency during therapy (16- or 24-hour). Two patients had hyperhomocysteinaemia (excess blood level of homocysteine), a condition associated with cardiovascular problems and neuropathy.

Of note, no patient elected to return to 16-hour infusion due to difficulty managing the pump, or technical difficulties with the jejunal tube.

Overall, if future studies confirm these findings, “24-[hour] LCIG may offer a novel approach to the treatment of troublesome dyskinesias which persist despite an adequate trial of 16-[hour] therapy,” researchers wrote.

Although further research is necessary to assess the mechanisms involved, the researchers hypothesized that the benefits with 24-hour treatment in patients not responding to 16-hour infusion may be due to continuous levodopa delivery to the brain.

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