Caffeine for Motor Manifestations of Parkinson's Disease
Schlüsselwörter
Abstrakt
Beschreibung
Caffeine has been in widespread use for centuries, and is the commonest psychostimulant used worldwide. In Canada, estimates of mean daily intake for a 70 kg person range from 200-450 mg. The main sources of caffeine ingestion are in beverages - depending on brewing technique a typical cup of drip-filtered coffee can contain between 100 and 150 mg of caffeine (gourmet drip coffees contain up to 300 mg and espresso preparations generally contain much less caffeine). Black tea contains between 30 and 50 mg, and lower amounts of caffeine are found in soft drinks, green teas, and chocolate. Caffeine is a substance with a well-defined effect and side-effect profile, and in general it is very well tolerated. Side effects can include irritability, insomnia, enhancement of physiologic tremor, and stomach upset. Abrupt withdrawal from caffeine can cause headache and excessive sleepiness. Caffeine can exacerbate pre-existing supraventricular tachycardia. Multiple large-scale epidemiologic studies have not found evidence for adverse health effects with long-term moderate use of caffeine. Caffeine has a T-max of approximately 1 hour and readily crosses the blood brain barrier. It has first order kinetics. Plasma half life estimates range from 3-6 hours, increased in the case of pregnancy or severe liver disease. Drug interactions are uncommon: Caffeine withdrawal may cause lithium toxicity, and caffeine increases clozapine levels.
CNS effects of caffeine are mainly due to antagonism of the A1 and A2A adenosine receptors, (A2A predominates in the striatum). Potential effects upon motor manifestations of PD are predominantly related to the antagonistic action of adenosine on dopamine release in the striatum. Partial tolerance to CNS effects is common, and begins to occur within one week (tolerance is more pronounced for the A1 receptor, suggesting that motor changes may show less tolerance). If effective for PD, caffeine has the potential to be a very important advance for patient care, for numerous reasons. First of all, it has been in widespread use for centuries, so the long-term safety has been determined. Caffeine is widely available as tablets which are very inexpensive (i.e. less than 25 cents per tablet), potentially resulting in substantial cost savings for patients and health-care planners. Caffeine also has the potential (as yet unproven) to treat non-motor manifestations of PD, particularly excessive daytime somnolence.
Termine
| Zuletzt überprüft: | 03/31/2015 |
| Zuerst eingereicht: | 08/25/2010 |
| Geschätzte Einschreibung eingereicht: | 08/26/2010 |
| Zuerst veröffentlicht: | 08/29/2010 |
| Letztes eingereichtes Update: | 04/14/2015 |
| Letztes Update veröffentlicht: | 04/15/2015 |
| Tatsächliches Startdatum der Studie: | 07/31/2010 |
| Geschätztes primäres Abschlussdatum: | 01/31/2011 |
| Voraussichtliches Abschlussdatum der Studie: | 01/31/2011 |
Zustand oder Krankheit
Intervention / Behandlung
Drug: Caffeine
Phase
Armgruppen
| Arm | Intervention / Behandlung |
|---|---|
| Experimental: Caffeine Each patient will take pills twice per day containing 100-200 mg of caffeine (as synthetic caffeine alkaloid). Patients will be instructed to take whatever caffeine-containing beverages they are accustomed to taking, without changing their habitual schedule (note that all will be taking <200 mg per day). Caffeine intake will be assessed at each visit. Patients will continue their usual PD medications, without change in dose or timing for the entire duration of the study. Medication will be provided in pre-packaged dosettes. | Drug: Caffeine The following intervention will be provided for six consecutive weeks:
Week 1 (100 mg BID), Week 2 (200 mg BID), Week 3 (300 mg BID), Week 4 (400 mg BID), Week 5 and 6(500 mg BID). At the conclusion of the study, patients will decrease their dose by 100 mg BID every other day, until caffeine is stopped. This gradual reduction will be to prevent withdrawal symptoms. If a patient experiences a dose-limiting event, they will be terminated from the study, and will withdraw from the medication in the same manner. If dose-limiting events occur between visits, patients will be encouraged to decrease the caffeine dose back to the previously-tolerated dose until in-person assessment can be performed. |
Zulassungskriterien
| Altersberechtigt für das Studium | 18 Years Zu 18 Years |
| Studienberechtigte Geschlechter | All |
| Akzeptiert gesunde Freiwillige | Ja |
| Kriterien | Inclusion Criteria: 1. Subject has been diagnosed with idiopathic Parkinson's disease (stage I - IV Hoehn and Yahr) Exclusion Criteria: 1. Estimated daily caffeine intake of more than 200 mg per day. 2. Subject has dementia (MMSE < 26/30) and ADL impairment secondary to cognitive loss, inability to understand consent process. 3. Changes to antiparkinsonian medications in last 4 weeks or changes will be required during the period of the study protocol. 4. Contraindication to caffeine use: 1. Uncontrolled hypertension (systolic bp >170 or diastolic bp >110 on two consecutive readings) 2. Use of lithium or clozapine 3. Pre-menopausal women who are not using effective methods of birth control 4. Current use of prescribed alerting agents such as modafinil and methylphenidate 5. Active peptic ulcer disease 6. Supraventricular cardiac arrhythmia 7. Previous adverse reaction to caffeine which either required admission to hospital,or after which the patient was directly advised by a physician to not use caffeine. |
Ergebnis
Primäre Ergebnismaße
1. Tolerability [6 weeks]
Sekundäre Ergebnismaße
1. Epworth Sleepiness Scale (ESS) [6 weeks]
2. Unified Parkinson Disease Rating Scale(UPDRS): Part II [6 weeks]
3. Timed Up and Go (TUG) [6 weeks]
4. Clinical Global Impression of Change [6 weeks]
5. Pittsburgh Sleep Quality Index [6 weeks]
6. Fatigue Severity Scale [6 weeks]
7. The Parkinson's Disease Questionnaire - PDQ-39 [6 weeks]
8. Beck Depression Inventory [6 weeks]
9. Beck Anxiety Inventory [6 weeks]
10. UPDRS: Part I,II,IV [6 weeks]
