Objective: To investigate the efficacy and safety for neuroprotection and disease modifying effect in  selegiline(SL) or zonisamide(ZN) by using UPDRS, PDQ-39 and DAT -SPECT  in patients with Parkinson’s disease(PD) undergoing pre-medication with L-dopa/DCI(LD).

Background: Many clinical trials have been conducted in the treatment of PD, but few have demonstrated disease-modifying effects. We targeted SL and ZN, which have MAOB inhibitory effects, and compared the change of DAT-SPECT and clinical scale to see if the combination of these drugs with L-dopa monotherapy could suppress disease progression .

Method: A total of 120 patients with PD were randomly allocated onto the following one year treatments of three groups; (1) LD alone, (2) LD+SL, and (3) LD+ZN. The percentage change in SBR ​​from ¹²³I-FP-CIT SPECT, change in UPDRS Part II- III and PDQ-39 scores (final – enrollment) in three groups were examined.

Results: The decrease ratio in SBR ​​(mean [95%CIs]) was 18.55 [5.94, 31.17] in LD, 9.05 [2.05, 16.05] in +SL, and 8.88 [-3.42, 21.18] in +ZN group. Both +SL and +ZN group had significantly lower SBR reduction rates than LD group, since the difference from LD was -10.62 [-25.28, 4.03] (p=0.079) in +SL, and -10.16 [-25.15, 4.82] (p=0.154) in +ZN group. The score changes in UPDRS Part II were 0.11 [-1.00,1.22], -0.25 [-0.86, 1.36], and -0.31 [-1.69, 1.08], and those in Part III score were -0.43 [-2.15, 1.28], -2.20 [-4.01, -0.39], and -1.49 [-3.70,0.73] in LD, +SL, and +ZN group, respectively. The change in PDQ-39 summary index was 1.56 [-1.40, 4.51], 0.90 [-2.14,3.93], and 3.41 [0.61,6.22] in LD, +SL and +ZN group, respectively. In PDQ-39 sub-items, motor score significantly worsened in LD (-4.80 [-9.08, -0.52]) and +ZN (-5.83 [-11.66, -0.00]), but not in +SL group (1.73 [-2.89, 6.35]). Communication score significantly worsened in LD group (3.60 [0.56, 6.64]), but not in +SL (2.35 [-1.31, 6.01]) or +ZN group (3.01 [-1.42, 7.44]).

Conclusion: Selegiline or zonisamide have been suggested to have neuroprotective effects on dopamine neurons in patients with early PD. Motor function also tended to be preserved in both +SL and +ZN groups compared to LD alone group. Regarding QOL, mobility tended to be maintained in +SL group, and communication tended to be maintained in +SL and +ZN groups.

Allocation, demographics and study protocol

Chronological change of SBR in DAT-SPECT

Change of MDS-UPDRS Part 2&3 scores

The score change of PDQ-39 subitems

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-multi-center-randomized-controlled-study-of-the-add-on-effect-of-selegiline-or-zonisamide-to-l-dopa-dci-therapy-in-parkinsons-disease-datsz-pd-study/