A Brain Imaging Study of Opioid (Morphine) and Non-opioid (Ketorolac) Conditioning Effects

Healthy Controls Clinical Trial

Official title:

A Brain Imaging Study of Opioid (Morphine) and Non-opioid (Ketorolac) Conditioning Effects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01576276
• Other study ID #: 2011P000358
• Status: Completed
• Phase: N/A
• Start date: April 2012
• Est. completion date: February 2017

Study information

• Verified date: May 2018
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Healthy right-handed volunteers aged 21 to 50 needed for a research study of the effects of morphine and ketorolac on brain activity in response to pain stimuli as measured by functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET). Study will be conducted on six separate days not requiring an overnight stay in the hospital.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 50 Years

Eligibility

Inclusion Criteria:

1. Healthy male and female adults, aged 21-50

2. No contraindications to fMRI scanning

3. Within 15% of normal BMI

4. Right handed (dominant hand is right hand)

5. Have taken an opioid drug at least once in the past (for example, after a surgery)

Exclusion Criteria:

1. Current or past history of major medical, neurological, or psychiatric illness

2. Women who are pregnant or breast feeding, have gone through menopause, or have irregular menstrual cycles (length of cycle must be within 26 to 32 days)

3. Contraindications to morphine administration:

• i) Hypersensitivity to morphine or other phenanthrene-derivative opioid agonists (codeine, oxycodone, etc.), morphine salts, or any component of the product

• ii) Concomitant use of other CNS depressants including antihistamines or alcohol

• iii) History of drug or alcohol abuse

• iv) History of head trauma

• v) History of liver problems

• vi) Pre-existing respiratory conditions (ex. COPD, asthma)

• vii) Current use of any drugs that interact with morphine

4. Contraindications to ketorolac administration

• i) Allergic-type reaction, or urticaria in response to exposure to aspirin or other NSAIDS

• ii) Concomitant aspirin or NSAID use

• iii) Hypersensitivity previously demonstrated to ketorolac tromethamine or to any product component

• iv) Peptic ulcer disease (active or history), or other gastrointestinal problems

• vi) Current use of any drugs that interact with ketorolac (ex. heparin/warfarin)

• vii) History of bleeding disorder

• viii) Low body weight, under 50 kg

5. Contraindications to fMRI scanning (including cardiac pacemaker, metal implants, claustrophobia, pregnancy)

6. Contraindications to either of the emergency medications (Ondansetron or Narcan)

7. History of head trauma

8. High blood pressure (>140 systolic, >90 diastolic)

9. History of impaired urinary elimination

10. Major kidney problems, bleeding problems, severe dehydration, or recovering from a recent surgery (within past year).

11. Instability of responses to experimental pain (see Study Procedures Section)

12. History of asthma

13. History of diabetes

14. Liver Function Test results greater than 2.5 times the upper limit of normal (ULN) at Screening

15. History of smoking (past or current)

16. Use of psychotropic drugs, hormone treatments (including hormonal birth control) within 1 year

17. Non-fluent speaker of English

18. Positive urine drug screen (i.e. positive on any of the 10 measures tested, including cocaine, marijuana, opiates, amphetamines, methamphetamines, phencyclidine, barbiturates, benzodiazepines, methadone, and tricyclic antidepressants)

Related Conditions & MeSH terms

• Healthy Controls

Intervention

Radiation:
• Integrated MR-PET scan
Integrated MR-PET scan using [11C]diprenorphine

Drug:
• Ketorolac
3 administrations of ketorolac over course of study

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Charlestown	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	fMRI Signal Changes	Obtain information about brain activity, including BOLD (Blood-oxygen-level dependent) signal, using an fMRI system. Data analysis was applied using SPM 12 with a standard pipeline.	one day
Primary	Pain Ratings	The primary endpoint was the morphine and ketorolac conditioning effects as indicated by subjective pain rating changes between pain only (a control condition with no injection of glucose, but subject's did see an image of an hour glass displaying how much time they had before receiving a painful stimulus) and pain+glucose (subjects received a glucose injection accompanied by an injection schematic followed by a painful stimulus) within the morphine and ketorolac groups. We used the Gracely pain rating scale (ranging from 0, no sensation to 20, extremely painful).	One day