Dextroamphetamine Substitution for Amphetamines Dependence: A Randomized Controlled Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Helse Bergen HF

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

18 Sep 2024 → ongoing

Decision date (initial)

2024-03-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

KLINBEFORSK (National strategic funding)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

a) To assess the impact of 12 weeks daily prescribed oral dextroamphetamine versus placebo on illicit amphetamines use and b) the total amount of amphetamines use in amphetamine-dependent patients undergoing opioid agonist treatment.

Secondary objectives 8

1. To assess the impact of DXA on mental health at 12 weeks
2. To assess the impact of DXA on physical health at 12 weeks
3. To assess the impact of DXA on quality of life at 12 weeks
4. To assess the impact of DXA on cognitive functioning at 12 weeks
5. To assess the impact of DXA on treatment adherence at 12 weeks
6. To assess the impact of DXA on comorbid substance use at 12 weeks
7. To assess the impact of DXA on criminal activity at 12 weeks
8. To assess the impact of DXA on private economy at 12 weeks

Conditions and MedDRA coding

Comorbid dependencies to amphetamines and opioids

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Be ≥18 age ≤65 years inclusive, at the time of signing the informed consent.
2. Overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
3. Dependent on amphetamines according to ICD-10 and an average frequency of use ≥3 days a week during the last 28 days.
4. If female and child-bearing potential, contraceptive should be used consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Non-pregnancy should be confirmed by a test if indicated .
5. Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
6. The eligibility will be determined by clinical assessment with a medical doctor.

Exclusion criteria 7

1. Contraindications pointed in the IPB (concomitant use of MAO-inhibitors or less than 14 days after the last dose of these drugs; symptomatic cardiovascular diseases (QTc>500 ms, persistent moderate to severe hypertension i.e. blood pressure [BP]≥140/90 mm Hg not controlled by a single anti-hypertensive agent (see Section 8.3.2.), prior myocardial infarction or stroke, advanced atherosclerosis); glaucoma; known hyperthyroidism or biochemical profiles from blood samples indicating of that; moderate or severe renal failure (i.e. GFR<100 ml/min/1,73 m²); agitation conditions.
2. Concomitant treatment with prescribed centrally acting stimulants (e.g. for ADHD).
3. Concurrent participation in other clinical studies when undergoing medication interventions.
4. Diagnostic assessments indicative for following conditions; ICD-10 diagnosis of multiple substances overdoses during the past three months (F10.0-19.0) based on medical records; ICD-10 diagnosis of a psychosis spectrum disorder (F20-29), or substance induced psychosis (F10.5-F19.5), or affective psychosis (F30, F31, F32.3) based on medical records if these conditions have been under treatment the last six months, or a score of ≥4 on the following psychosis symptoms items on the PANSS: P1 – delusions; P3 – hallucinatory behavior; A9 – unusual thought content (based on the interview conducted at the time of screening); seizure; recent high risk of agitation and violent behavior e.g. dissocial personality disorders or affective disorders; severe cognitive impairment (based on clinical assessments or using HASI if indicated); suicidality (based on clinical assessments).
5. Challenges related to ability to understand, consent, or willingness to collaborate in follow-up of the study and its protocol.
6. Inability to complete study procedures (e.g. travel plans or likely incarceration).
7. Pregnancy or breastfeeding.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. a) The differences in the proportion positive urinary tests on illicit amphetamines and b) mean total self-reported quantity* (mg/day) of amphetamines use between the intervention and control arm during 12-week trial (cumulative data). * Dosage of illicit amphetamines will be converted to prescribed dexamphetamine dosage and added to the prescribed dosage

Secondary endpoints 17

1. Psychological distress (SCL-10)
2. Psychosis (PANSS: P1, P3, A9)/ LSHS-E
3. ADHD (ASRS)
4. Quality of life (EQ-5D-5L)
5. Executive cognitive performance (TMT B)
6. Fatigue (FSS-3)
7. Treatment satisfaction (VAS)
8. Adherence to OAT (days of drop-out)
9. Days of use of illicit amphetamines (at the end of the 12 weeks)
10. Days of use and porpotion of other illicit substances and alcohol (self-reports and urinary tests)
11. Injection-related infections (medical records) and HCV RNA incidence
12. Violence risk (BVC)/(PANSS: P4 and P7)
13. Criminality (criminal actions)
14. Sleep (ISI)
15. Private economy (total and health-related)
16. Craving and withdrawals to amphetamines
17. Sucidality risk at the end of 12-week trial.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Helse Bergen HF

Sponsor organisation

Helse Bergen HF

Address

Haukelandsveien 22

City

Bergen

Postcode

5021

Country

Norway

Scientific contact point

Organisation

Helse Bergen HF

Contact name

Fatemeh Chalabianloo

Public contact point

Organisation

Helse Bergen HF

Contact name

Fatemeh Chalabianloo

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 27 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications