Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression.
BACKGROUND
Pramipexole and levodopa are effective medications to treat motor symptoms of early Parkinson disease (PD). In vitro and animal studies suggest that pramipexole may protect and that levodopa may either protect or damage dopamine neurons. Neuroimaging offers the potential of an objective biomarker of dopamine neuron degeneration in PD patients.


OBJECTIVE
To compare rates of dopamine neuron degeneration after initial treatment with pramipexole or levodopa in early PD by means of dopamine transporter imaging using single-photon emission computed tomography (SPECT) with 2beta-carboxymethoxy-3beta(4-iodophenyl)tropane (beta-CIT) labeled with iodine 123.


METHODS
Substudy of a parallel-group, double-blind randomized clinical trial.


METHODS
Eighty-two patients with early PD who were recruited at 17 clinical sites in the United States and Canada and required dopaminergic therapy to treat emerging disability, enrolled between November 1996 and August 1997.


METHODS
Patients were randomly assigned to receive pramipexole, 0.5 mg 3 times per day with levodopa placebo (n = 42), or carbidopa/levodopa, 25/100 mg 3 times per day with pramipexole placebo (n = 40). For patients with residual disability, the dosage was escalated during the first 10 weeks, and subsequently, open-label levodopa could be added. After 24 months of follow-up, the dosage of study drug could be further modified.


METHODS
The primary outcome variable was the percentage change from baseline in striatal [(123)I]beta-CIT uptake after 46 months. The percentage changes and absolute changes in striatal, putamen, and caudate [(123)I]beta-CIT uptake after 22 and 34 months were also assessed. Clinical severity of PD was assessed using the Unified Parkinson Disease Rating Scale (UPDRS) 12 hours off anti-PD medications.


RESULTS
Sequential SPECT imaging showed a decline in mean (SD) [(123)I]beta-CIT striatal uptake from baseline of 10.3% (9.8%) at 22 months, 15.3% (12.8%) at 34 months, and 20.7% (14.4%) at 46 months-approximately 5.2% per year. The mean (SD) percentage loss in striatal [(123)I]beta-CIT uptake from baseline was significantly reduced in the pramipexole group compared with the levodopa group: 7.1% (9.0%) vs 13.5% (9.6%) at 22 months (P =.004); 10.9% (11.8%) vs 19.6% (12.4%) at 34 months (P =.009); and 16.0% (13.3%) vs 25.5% (14.1%) at 46 months (P =.01). The percentage loss from baseline in striatal [(123)I]beta-CIT uptake was correlated with the change from baseline in UPDRS at the 46-month evaluation (r = - 0.40; P =.001).


CONCLUSIONS
Patients initially treated with pramipexole demonstrated a reduction in loss of striatal [(123)I]beta-CIT uptake, a marker of dopamine neuron degeneration, compared with those initially treated with levodopa, during a 46-month period. These imaging data highlight the need to further compare imaging and clinical end points of PD progression in long-term studies.
D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D052160:Benzothiazoles; D001921:Brain / Q000000981:diagnostic imaging*; D003042:Cocaine / Q000031:analogs & derivatives; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000627:therapeutic use*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008875:Middle Aged; D009410:Nerve Degeneration; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D000077487:Pramipexole; D019275:Radiopharmaceuticals; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D013844:Thiazoles / Q000627:therapeutic use*; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
D000978:Antiparkinson Agents; D052160:Benzothiazoles; D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; D013844:Thiazoles; D007980:Levodopa; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D000077487:Pramipexole; D003042:Cocaine; D004298:Dopamine