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A comparative randomized study for the evaluation of the overlaying effect of Selegiline or Zonisamide over Levodopa in Parkinson's disease

The DAT-SPECT study for the benefit of Selegilline or Zonisamide in Parkinson's Disease (DATSZ-PD study)

125

Baseline characteristics of 120 participants, excluding 5 partipants who withdrew consent. 1. LD group [n=37]: m/f 25/12, age 70.2 (6.8), MMSE 28.1 (1.8) 2. FP group [n=43]: m/f 24/19, age 69.4 (6.6), MMSE 28.5 (1.8) 3. ZN group [n=40]: m/f 17/23, age 70.1 (5.9), MMSE 27.9 (2.0)

1. LD group: 38 allocated, 1 withdrawn, 37 eligible, 0 excluded, 37 FAS 2. FP group: 44 allocated, 1 withdrawn, 43 eligible, 0 excluded, 43 FAS 3. ZN group: 43 allocated, 3 withdrawn, 40 eligible, 1 excluded, 39 FAS

LD group: nausea and diplopia in 1 case (2.7%) each. FP group: nausea and orthostatic hypotension in 1 case (2.3%) each. ZN group: depression in 2 cases (5%), muscle weakness, somnolence, dizziness, anorexia, anger, anxiety disorder, insomnia, and abdominal discomfort in 1 case (2.5%) each. No serious adverse events were observed during the study period.

The primary endpoint, rate of decrease in SBR (sum of two sides) (mean [95% confidence interval (CI)]), was 18.55 [5.94, 31.17] in the LD group, 9.05 [2.05, 16.05] in the FP group, and 8.88 [-3.42, 21.18] in the ZN group. Point estimates and 95% CIs for the between-group difference from the LD group were 9.50 [-4.75, 23.76] in the FP group and 9.67 [-7.64, 26.99] in the ZN group. Adjusted for age, the difference was -10.62 [-25.28, 4.03] (p = 0.079) in the FP group, and -10.16 [-25.15, 4.82] (p = 0.154) in the ZN group: both the FP group and the ZN group had significantly lower SBR reduction rates than LD group. As secondary endpoints, changes in UPDRS Part II (postintervention-baseline) [95% CI] were 0.11 [-1.00, 1.22] in the LD group, -0.25 [-1.36, 0.86] in the FP group, and -0.31 [-1.69, 1.08] in the ZN group. The changes in Part III were -0.43 [-2.15, 1.28] in the LD group, -2.20 [-4.01, -0.39] in the FP group, and -1.49 [-3.70, 073] in the ZN group, with significant improvement only in the FP group. Changes in the PDQ-39 summary index (postintervention-baseline) [95% CI] were 1.56 [-1.40, 4.51] in the LD group and 0.90 [-2.14, 3.93] in the FP group, and 3.41 [0.61, 6.22] in the ZN group. In the subdomains, the mobility scores were significantly worse in the LD group (4.80 [0.52, 9.08]) and the ZN group (5.83 [0.00, 11.66]), but were not in the FP group (1.73 [-2.89, 6.35]). Communication was significantly worse in the LD group (3.60 [0.56, 6.64]), but there was no significant difference in the FP group (2.35 [-1.31, 6.01]) and ZN group (3.01 [-1.42, 7.44]).

Selegiline or zonisamide have been suggested to have protective effects on dopamine neurons in patients with early Parkinson's disease. Motor function also tended to be preserved in both the selegiline and zonisamide groups. Regarding QOL, mobility tended to be maintained in the FP group, and communication tended to be maintained in the selegiline and zonisamide groups.

Mar. 31, 2024

No

None

https://jrct.mhlw.go.jp/latest-detail/jRCTs051180098

Ito Hidefumi

Wakayama Medical University Hospital

811-1 Kimiidera,Wakayama-shi,Wakayama, Japan

ito@wakayama-med.ac.jp

Koh Jinsoo

Wakayama Medical University Hospital

811-1 Kimiidera,Wakayama-shi,Wakayama, Japan

+81-73-447-2300

jinsoo@wakayama-med.ac.jp

Complete

Jan. 01, 2016

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

(1) Those who are at age between 55 and 79 years.
(2) The patients should be within 3 years after the onset of motor symptoms.
(3) The patients should be treated with levodopa/DCI within 3 months and with levodopa/DCI exclusively 28 days right before starting the trial.
(4) The dose of levodopa/DCI should be taken from 150mg/day to 300mg/day.
(5) The participant's score of MMSE should be 25 or higher.
(6) The patient should be judged by attendant doctor to be appropriate for registration.
(7) The agreement with the study should be obtained by the document.

(1) Those who had been treated with the anti-parkinsonian drugs except levodopa/DCI for more than 1month.
(2) Those who are in pregnancy, or possible to be pregnant or those who are in the breast-feeding.
(3) Those who have taken antidepressant and/or anti-psychotic drugs.
(4) Those who have a history of stroke and cerebrovascular disorders.
(5) Those who had a history of epilepsy or those who are in treatment of epilepsy.
(6) Those who have a history of alcohol intoxication, or have the treatment for alcoholic abuse.
(7) Those who have severe comorbidity (liver dysfunction, renal dysfunction and endocrinological disorders).
(8) Those who have a familial history of Parkinson's disease.
(9) Those who have a history of allergic reaction with 123I-ioflupane.

Both

Parkinson's disease

L-Dopa/DCI only : The drug is administered per oral at 300 mg/day. The treatment is started within 14 days after registration and continued until day 365.
L-Dopa/DCI + selegiline : L-Dopa/DCI is administered per oral at 300 mg/day and selegiline is administered at 5 mg/day. The treatment is started within 14 days after registration and continued until day 365.
L-Dopa/DCI + zonisamide : L-Dopa/DCI is administered per oral at 300 mg/day and zonisamide is administered at 25 mg/day. The treatment is started within 14 days after registration and continued until day 365.

034034

The percent change of SBR of DAT-SPECT from the first evaluation to the final evaluation at 1 year

- Change in UPDRS score (PartII, PartIII)
- Change in PDQ-39 score

+81-73-441-0896

Jan. 30, 2019

none